Prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma

The Clinic of Laserplastics, Riga LV, Latvia.
Stomatologija / issued by public institution "Odontologijos studija" ... [et al.] 01/2011; 13(2):49-54.
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ABSTRACT
OBJECTIVE. To describe the prognostic factors and epidemiological characteristics of cutaneous and mucosal head and neck melanoma and to identify the variables associated with mortality from this disease. MATERIAL AND METHODS. Patients treated for head and neck melanoma in the Oncology Centre of Latvia, Riga during a 10-year period were identified. Records from 124 cases were analyzed in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark invasion level was viewed. Disease specific survival rates were calculated. The frequencies of all study variables and their 95% confidence intervals were determined. Kaplan-Meier survival curves were produced to illustrate the survival differences for each variable. RESULTS. The patients' mean age was 67.36 years. The study included 81 females (65.32%) and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma was the cheek - 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutaneous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating (38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal melanoma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a ten year period are decreasing. CONCLUSION. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and ulceration carried a relevant risk of poor prognosis.

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Stomatologija, Baltic Dental and Maxillofacial Journal, 2011, Vol. 13, No. 2 49
Prognostic Factors and Epidemiological Characteristics
of Cutaneous and Mucosal Head and Neck Melanoma
Anna Berzina, Kristine Azarjana, Ingrida Cema, Dace Pjanova, Alexander Rivosh
SCIENTIFIC ARTICLES
SUMMARY
The objective. To describe the prognostic factors and epidemiological characteristics of
cutaneous and mucosal head and neck melanoma and to identify the variables associated with
mortality from this disease.
Material and methods. Patients treated for head and neck melanoma in the Oncology Centre
of Latvia, Riga during a 10-year period were identi ed. Records from 124 cases were analyzed
in a descriptive, retrospective study. For each patient, information regarding age, sex, tumor
anatomic site, as well as ulceration, histological tumor subtypes, Breslow thickness and Clark
invasion level was viewed. Disease speci c survival rates were calculated. The frequencies of
all study variables and their 95% con dence intervals were determined. Kaplan-Meier survival
curves were produced to illustrate the survival diferences for each variable.
Results. The patients mean age was 67.36 years. The study included 81 females (65.32%)
and 43 males (34.67%). The prevalent anatomical site for cutaneous head and neck melanoma
was the cheek 49% (n=55) and the intraocular site for mucosal melanoma (61.5%). A high
percentage of thick cutaneous melanoma was detected. In 53 cases (47.3%) out of 112 cutane-
ous melanoma the tumor ulceration was found. Nodular melanoma subtype was predominating
(38%). The incidence of cutaneous melanoma has increased unequally whereas mucosal mela-
noma of the head and neck is an uncommon cancer and the incidence rates in Latvia during a
ten year period are decreasing.
Conclusion. Female sex, advanced age, facial skin, tumor thickness, nodular subtype and
ulceration carried a relevant risk of poor prognosis.
Keywords: head and neck melanoma, survival, mortality.
SCIENTIFIC ARTICLES
Stomatologija, Baltic Dental and Maxillofacial Journal, 13: 49-54, 2011
INTRODUCTION
Melanoma is a potentially fatal cancer derived from
abnormally proliferating melanocytes, although the pro-
cess called melanomagenesis has not yet been fully
understood [1]. Cutaneous melanoma only accounts for
3% of all skin tumors, however this malignant cancer
presents high mortality rates, accounting for 75% of all
deaths due to cutaneous malignant neoplasms [2,3,4].
The incidence of cutaneous melanoma has in-
creased dramatically since the early 1970s [5]. The
rates of incidence and mortality rise in the Caucasians
with each year all over the world [6,7,8,9]. The reason
for these increases is probably related to changes in
peoples habits, including types of leisure and clothes,
which in case of head and neck melanoma expand
the in uence of ultraviolet light [10,11,12,13]. Fac-
tors like the relationship between skin immunity and
melanoma development as well as genetic predisposi-
tion are also known [14].
Although cutaneous and mucosal head and neck
melanoma (CMHNM) is not the leading anatomical
site, the tumor arising from this region has a worse
prognosis and require better understanding of the
factors that play a role in the disease.
The aim of the study is to describe the epide-
miological features of cutaneous and mucosal head
and neck melanoma and to identify factors associated
1
The Clinic of Laserplastics, Riga, Latvia
2
Riga Stradins University, Doctoral Studies
3
Riga Stradins University; The Oncology Center of Latvia
4
Latvian Biomedical Research and Study Centre
5
University of Latvia, Faculty of Computing
Anna Berzina
1
Dr. Med.
Kristine Azarjana
2
PhD student
Ingrida Cema
3
Dr. Habil. Med., prof.
Dace Pjanova
4
PhD, researcher
Alexander Rivosh
5
MSc. comp., researcher
Address correspondence to Dr. Anna Berzina, Vairoga Street 38-1,
Riga LV-1039, Latvia.
E-mail address: berzina.anna@gmail.com
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50 Stomatologija, Baltic Dental and Maxillofacial Journal, 2011, Vol. 13, No. 2
A. Berzina et al. SCIENTIFIC ARTICLES
Fig. 1. Number of new cases of cutaneous and mucosal head
and neck melanoma in a ten year period
measurement of tumor thickness according to this
method is one of the most signi cant microscopic
parameters to predict metastasis [18,19]. The Clarks
levels of melanoma invasion represent a descrip-
tion of the magnitude of invasion of the tumor. It
is de ned through the different microscopic levels
of the skin from the epidermis to the subcutaneous
tissue [18]. The data included also patients vital
status (alive or dead). In addition, the patients were
separated into two groups: up to 60 years and over
60 years. Descriptive statistics were calculated and
95% con dence intervals were de ned for all the
variables. Such measure as age was summarized
using means and standard deviations, while cat-
egorical measures were summarized in counts and
percentages. Death from melanoma was the survival
outcome of interest. All the remaining were consid-
ered as censored. The Kaplan-Meier survival curves
were used to illustrate the differences of survival for
each categorical variable. Kaplan-Meier estimator
is designed to estimate the probability of an event
that eventually will occur for all patients, ie, death.
Statistical differences with a p value <0.05 were
considered signi cant [19].
RESULTS
The study group was composed of 43 males
(34.67%) and 81 women (65.32%). The mean age of
the cohort was 67.36 years, aged from 25 to 93 years
(standard deviation, 14.50 years). The mean age for
women exceeds the mean age of men, accordingly
69.55 to 63.23 years.
The number of new cases of CMHNM increased
irregularly from 12 cases in 1998 to 17 in 2007
(Figure 1).
Female patients were most of the cohort with
68.75% deaths compared with 31.25% in male pa-
tients. Females were more likely to die (con dence
interval, CI=0.51 to 0.82; p=0.68) (Figure 2).
The mean age of women patients with cutaneous
and mucosal head and neck melanoma in the rst
decade (year 1998 till 2002) (n=34) was 70.08 years,
while in the second analyzed decade (year 2003 till
2007), the mean age was 69.17 years (n=47). In rela-
tion to men patients, the mean age of the rst decade
was higher comparing to the second one, respectively
64.8 years and 62.0 years (n=15 and n=27).
The most frequent anatomical site of CMHNM
was the cheek (n=55, 49%), followed by the ear
(n=14, 13%) and neck (n=12, 11%). Melanoma was
least frequent on the lips, palate tonsil and hard palate
(n=1, 0.81% each) (Figure 3).
Patients with lesions of the scalp, neck and ear
Fig. 2. Difference in mortality between sexes
with mortality from this disease. By identi ying the
factors that affect survival of patients, we could in-
vent preventive and therapeutic strategies to change
the mortality rates from melanoma as well as con-
tribute towards better comprehension of the disease
[2,15,16,17]. In relation to mucosal melanoma, Bre-
slow thickness and Clark level data are typically not
applicable for this tumor, we tried to generalize the
epidemiological characteristics of this tumor.
MATERIALS AND METHODS
This is a retrospective, descriptive study. The re-
cords of 124 cases of CMHNM diagnosed as having
or treated between January 1, 1998, and December
31, 2007 were obtained from The Onclogy Centre of
Latvia, Riga. For each patient, information regarding
age, gender, tumor localization as well as ulceration,
histological subtypes, the predominant cell type,
melanoma Breslow thickness and Clark invasion
level was viewed. The depth of invasion of mela-
noma was categorized by objective measurement
Breslow thickness (measured in milimeters). The
Page 2
Stomatologija, Baltic Dental and Maxillofacial Journal, 2011, Vol. 13, No. 2 51
SCIENTIFIC ARTICLES A. Berzina et al.
were more likely to die, comparing to the anatomic
site of the face (Figure 4).
Nodular melanoma was the most common his-
tological feature and was diagnosed in 38.39% of
all cutaneous melanoma cases. Super cial spread-
ing melanoma was found in 8 cases (7.14%), lentigo
maligna melanoma in 6 cases (5.36%). Nearly half
of the cohort (49.11%) was histologically unclassi-
ed (Figure 5).
Of all morphological features, nodular melanoma
carried substantially worse prognosis in accordance
with patients survival (Figure 6).
The presence of ulceration was more frequently
found in women after the age of 60 years (n=25;
29.76%), whereas until the age of 60 years in 7 cases
(25%). In the group of patients under the age of 60,
males had the ulceration of tumor in 9 cases (32.14%),
but over the age of 60 14.29 % (12 cases). Ulcer-
ation was signi cantly associated with melanomas
prognosis (Figure 7).
Fig. 5. Distribution of the cutaneous melanoma cases, ac-
cording to the subtype of tumor
Fig. 4. The risk of mortality for cutaneous melanoma
Fig. 3. Number of cutaneous melanoma cases in relation to the primary lesion site
For the purpose of the analyses, tumor thickness
was categorized into 3 groups: thin (1 mm), interme-
diate (>1-3,9 mm) and thick (4 mm) melanoma. The
mean thickness of the primary tumors was 4.99 mm.
In 19 cases it was not possible to obtain such data.
Thick melanomas (4 mm) in the group of age over 60
years for both sexes were diagnosed predominantly,
correspondingly 45.67% (n=22) for women and in
8 cases (33.33%) for men. Younger patients (under
the age of 60) had characteristic of thick melanomas
to a lesser extent. Women were diagnosed with thick
melanomas in 7 cases (46.67%), whilst men in 8
cases (61.54%). The total amount of thick melanomas
was 45, out of which 16 cases (35.56%) in men and
29 cases (64.44%) in women. Thin tumors (1mm)
were characteristic of rarely occurence in the age
group of younger patients only one case (6.67%)
in women and accordingly 1 case (7.72%) in men. In
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52 Stomatologija, Baltic Dental and Maxillofacial Journal, 2011, Vol. 13, No. 2
the age group of 60 years and older thin melanomas
were diagnosed in 11 cases 13.33% (n=8) in women
and 12.5 % (n=3) in men (Figure 8).
Tumors with greater thickness had an unfavor-
able prognosis (Figure 9).
Clark invasion level V had the highest mortality.
The lesser the invasion level was, the more decreased
the mortality (Figure 10). In most cases (28%, n=32)
both gender patients Clark level was III. In 29% of
men patients (n=11) Clark invasion level was IV.
DISCUSSION
Melanoma is a potentially fatal malignant tumor
with increasing incidence over the last few decades
in many countries of the world [2,5,21,22]. Although,
head and neck anatomic location for melanoma was
not highlighted and described in every scienti c pa-
per mentioned above, the fact of steady increase in
the incidence of melanoma is mentioned in the vast
majority of corresponding scienti c papers, which is
A. Berzina et al. SCIENTIFIC ARTICLES
different from our data. The amount of patients with
cutaneous and mucosal head and neck melanoma in
Latvia is inconsistent and could not be described as
a persistent increase.
According to other authors, the mean age of
melanoma patients is 53.7 to 59 years [2,19,23,24],
thus playing a substantial role in loosing a prominent
amount of years of life. As we analyzed the head and
neck region of the body, contrary to some papers
mentioned above, patients with cutaneous and mu-
cosal head and neck melanoma in Latvia are featured
elderly. As prognosis worsens with increasing age,
patients drawn in our study are all subdued to a worse
prognosis concerning the survival and complications.
Numerous studies have demonstrated that male
melanoma patients outnumber females [7,8,15,21,25].
According to the Cancer Register of Latvia, the in-
cidence of melanoma in men patients in year 2009
was 6.2/100000, however in women 7.7/100000.
Comparatively this rate in year 1988 was 3.3/100
000 for both genders. Reduced melanoma incidence
Fig. 8. Distribution of the cases by patients age, according to
melanoma Breslow thickness
Fig. 9. Kaplan-Meier survival curve for differet Breslow thick-
ness melanomas
Fig. 6. Mortality from different subtypes of melanoma Fig. 7. Kaplan-Meier survival curve for ulcerated and non-
ulcerated melanomas
Page 4
Stomatologija, Baltic Dental and Maxillofacial Journal, 2011, Vol. 13, No. 2 53
rate in men probably is related to infrequent self
examination, as well as less pronounced participa-
tion in primary and secondary melanoma prevention
campaigns [26,27].
The authorities in the eld of melanoma claim
that head and neck melanoma carry the worst prog-
nosis, comparing with other anatomical sites [15,28].
Scalp, neck and ear melanoma has a poor prognosis,
which has been proven not only in other scienti c
studies [15,29], but also in ours. As head and neck
melanoma is localized in an anatomical site which can
be seen to any speciality of doctors, it should increase
the probability of being diagnosed early.
The prognosis of melanoma is very good if the
tumor is thin at the time of diagnosis. In this case
5-year survival is 95-97% [30]. The risk of metastasis
radically increases when melanoma is diagnosed in a
late stage (tumor Breslow thickness >4mm). Thereby,
early diagnosis of melanoma is invaluably essential
as it improves the prognosis of the disease. Having a
good knowledge in the epidemiologic characteristics
and prognostic factors of melanoma, primary and sec-
ondary prevention of this malignant tumor can be up-
graded. Tumor Breslow thickness is the most powerful
prognostic value [28], whilst increasing Clark invasion
SCIENTIFIC ARTICLES A. Berzina et al.
level also is associated with more frequent mortality
[15]. We found that Clark level of invasion V, thick
melanomas (Breslow thickness 4 mm) and ulcerated
tumors carried a signi cantly worse prognosis.
According to other authors super cial spreading
melanoma is the most frequent histopathologic tumor
subtype [2,21,25,28]. In our study nodular subtype of
melanoma was the most common and the cummula-
tive survival curve demonstrated the worse prognosis
for these patients.
Although cutaneous malignant melanoma is one
of the most preventable and treatable of cancers [30],
the mortality rates have risen during the past 20 years
[2,21,32]. In Latvia, in the year of 2008, 34 cases of
death due to body melanoma were recorded in male
gender, while 45 in women. Respectively, in the year
of 1988 - 11 cases of death in men and 22 in women.
Number of cases of death from head and neck melanoma
are instable and does not have a convincing tendency to
grow. During the period of 10 years that was analyzed
in our study, most of all death cases from head or neck
melanoma was found in the year of 2006 (n=5).
CONCLUSIONS
The prognosis of most of the analyzed cases
is poor, according to survival, local recurrence and
distant metastasis due to delayed diagnosis.
In our study we found the predominance of
female gender and advanced aged patients, as well
as nodular, ulcerated and thick melanomas, mostly
localized on the face - factors all of which carry a
relevant risk of poor prognosis.
ACKNOWLEDGEMENTS
This work is supported by the grant
EEZ09AP-38/08.
Azarjana K. is supported by a grant from
the European Social Fund (ESF) program no
Nr.2009/0147/1DP/1.1.2.1.2/09/IPIA/VIAA/009.
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  • [Show abstract] [Hide abstract] ABSTRACT: Background  Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma. Objectives  The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence. Methods  We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma. Results  The study showed a significant ascending trend in melanoma incidence in Latvia during the time period from 1998 to 2008 (ß = 1.83, 95% CI = 1.15-2.91, P = 0.011). Nodular melanoma was the most common tumour subtype with a frequency of 39.2%. Ulceration was present in 45.2% of melanomas. The mean Breslow thickness was 6.0 mm (6.8 mm) and no significant decline in median Breslow thickness was observed during the study period (P = 0.609). A better overall prognosis was detected for females in comparison with males (HR = 1.49; 95% CI = 1.22-1.81; P < 0.001). Conclusions  There is a steady increase in melanoma incidence in Latvia with the majority of melanomas diagnosed at late stages with poor prognosis for survival.
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  • [Show abstract] [Hide abstract] ABSTRACT: Aim: Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. Methods: The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. Results: A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (<25 years) parental age at birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. Conclusion: This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses.
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  • [Show abstract] [Hide abstract] ABSTRACT: Objective/HypothesisTo evaluate age as an independent prognostic factor in cutaneous head and neck melanoma. Study DesignProspective case-control study. Methods We selected 12,195 patients from the Surveillance, Epidemiology, and End Results database with cutaneous head and neck melanoma diagnosed from 2004 to 2009. Patients were stratified into ages 1 to 44 years, 45 to 64 years, and 65+ years. Meanwhile, stage was stratified into early (American Joint Committee on Cancer [AJCC] stage I-II) versus late (AJCC stage III-IV). We calculated overall survival and compared it to age-matched cancer-free controls to obtain overall relative survival. Finally, we performed a Cox multivariate regression by age and stage. ResultsAge had a statistically significant (P<.05) stratified decrease in overall survival for both early- and late-stage melanoma. However, we only found a statistically significant (P<.05) stratified decrease in overall relative survival for late-stage melanoma. Early-stage melanoma had no statistical difference in overall relative survival between the 45 to 64 years group and all other age groups studied. Finally, our multivariate Cox regression of stage, gender, race, and age found a hazard ratio [HR] of 2.005 (95% confidence interval [CI]: 1.493-1.693, P<.001) for the 45 to 64 years age group, and an HR of 4.174 (95% CI: 3.153-5.526, P<.001) for the 65+ years age group. Conclusions Age at diagnosis is a poor prognostic factor for patients with cutaneous head and neck carcinoma. It plays an important role in survival, with a linear increase in risk as age increases. This risk is clinically significant with patients ages 65+ years, having an HR four times the risk of patients 1 to 44 years old. Level of Evidence3b. Laryngoscope, 124:462-465, 2014
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