745825

research-article2017
CMSXXX10.1177/1203475417745825Journal of Cutaneous Medicine and SurgeryGhazawi et al

Original Article–Invited Submission

Journal of Cutaneous Medicine and Surgery

Distribution and Clustering of Cutaneous 1­–12

© The Author(s) 2017
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DOI: 10.1177/1203475417745825
https://doi.org/10.1177/1203475417745825

Canada During 1992 to 2010 jcms.sagepub.com

Feras M. Ghazawi1,2, Elena Netchiporouk2,

Elham Rahme3, Matthew Tsang1, Linda Moreau2,
Steven Glassman1 , Nathalie Provost4, Martin Gilbert5,
Sara-Elizabeth Jean6, Osama Roshdy2, Kevin Pehr2 ,
Denis Sasseville2, and Ivan V. Litvinov1,2

Abstract
Background: Clustering of patients with cutaneous T-cell lymphoma (CTCL) was reported in several jurisdictions around the
world. This rare cancer is known to affect spouses and in some cases multiple members of the same family. These combined
results suggest the existence of external disease triggers/promoters. We recently conducted the first comprehensive analysis
of CTCL incidence and mortality in Canada, which revealed case clustering in several regions.
Objectives: To extend our previous analysis on CTCL incidence across Canada and to provide all the collected data on
CTCL patient incidence in Canada during the period of 1992 to 2010.
Methods: Clinical parameters for patients with CTCL in Canada were analyzed using 2 independent population-based cancer
registries: Canadian Cancer Registry and Le Registre Québécois du Cancer. The CTCL incidence rates were examined on
different geographical levels, including provinces/territories, cities, and forward sortation areas.
Results: Our findings further corroborate our earlier observations of higher CTCL incidence in Newfoundland and
Labrador, maritime provinces (Nova Scotia and New Brunswick), and prairie provinces (Manitoba and Saskatchewan).
Also, most cities with high CTCL incidence were located in these provinces. Extensive mapping of high-incidence postal
codes supports case clustering in a number of communities that are located in the proximity of industrial centres and
seaports.
Conclusions: Detailed analysis of CTCL incidence in Canada is critical to fully understand the burden of this disease in our
country, to begin the search for a possible external trigger for this lymphoma, and to reform how health care resources are
distributed throughout the country to better serve Canadian patients with CTCL.

Keywords
cutaneous T-cell lymphoma (CTCL), incidence, geographic clustering, industrial exposure, transportation, seaports

Cancer is a leading cause of morbidity and mortality, with

more than 10 million new cases reported annually.1 It is esti-
1
Division of Dermatology, University of Ottawa, Ottawa, Ontario, Canada
2
mated that the minority (~10%) of all cancer cases are attrib- Division of Dermatology, McGill University Health Centre, Montréal,
Québec, Canada
utable to genetics alone, while the majority are related to 3
Division of Clinical Epidemiology, McGill University, Montréal, Québec,
environmental factors and human behaviours.1 Current evi- Canada
dence indicates that ~25% to 30% of all cancer-related mor- 4
Division of Dermatology, University of Montréal, Montréal, Québec,
tality is attributable to tobacco use, ~30% is due to diet, Canada
5
~15% is due to infections, and the remaining factors/triggers Division of Dermatology, Université Laval, Québec City, Québec, Canada
6
Division of Dermatology, University of Sherbrooke, Sherbrooke,
include radiation, stress, immunosuppression, and pollu- Québec, Canada
tion.1 Therefore, many malignancies are indeed preventable
with lifestyle modifications and by minimizing exposures to Corresponding Author:
Ivan V. Litvinov, Division of Dermatology, McGill University Health
harmful substances. Through rigorous research, a number of Centre, Rm. E02.6236, 1001 Decarie Blvd, Montréal, Québec H4A 3J1,
environmental factors and infectious agents implicated in Canada.
carcinogenesis were recently elucidated. Throughout this Email: ivan.litvinov@mcgill.ca
2 Journal of Cutaneous Medicine and Surgery 00(0)
discovery process, epidemiologic studies were proven to be
a powerful method that can estimate the occurrence of dis-
eases in a given population. There are several types of epide-
miologic studies, including cohort, case-control, ecologic,
and cluster studies. Notably, cluster studies identify a non-
random distribution of patients and can implicate environ-
mental factors as potential causes of a disease.
Skin, lungs, and gastrointestinal tract are the 3 main organ
systems that are constantly interfacing with the environment.
Therefore, it is not surprising that many malignancies in
these organs are triggered by external and often preventable
causes such as smoking and asbestos responsible for lung
cancers and mesotheliomas, respectively. Similarly, expo-
sure to polycyclic aromatic hydrocarbons was implicated as
a cause for colon cancers, and Helicobacter pylori is known
to cause gastric cancers. In recent years, research has estab-
lished a definitive link between several etiologic agents and
skin cancers. Ultraviolet radiation was proven to cause mela-
nomas, and viruses including human papillomavirus (HPV)
and Merkel cell polyomavirus (MCPyV) were shown to
cause squamous cell and Merkel cell cancers, respectively.
Indeed, skin is a highly complex and dynamic immune organ
and contains lymphocytes that protect the body from exter-
nal pathogens. Disruption of molecular pathways in skin
lymphocytes by bacterial, viral, or environmental factors is
known to lead to cutaneous lymphomas.2 Not surprisingly,
for a number of these malignancies, bacterial or viral agents
were shown to drive carcinogenesis and cancer progression.
For instance, recent evidence indicates that primary cutane-
ous marginal zone B-cell lymphomas can be triggered by
Borrelia burgdorferi.2 Also, for a number of systemic T-cell
lymphomas that often manifest with skin lesions such as
adult T-cell leukemia/lymphoma or natural killer T-cell lym-
phoma of nasal type, viral etiology and involvement of
human T-cell lymphotropic virus type 1 (HTLV-1) or Epstein-
Barr virus (EBV), respectively, have been extensively
documented.3,4
Cutaneous T-cell lymphoma (CTCL) is the most common
skin lymphoma and represents a heterogeneous group of
non-Hodgkin lymphomas, yet the precise pathogenesis by
which CTCL develops remains poorly elucidated.5-10 Patients
with CTCL typically present with thickened plaques or
patches that may clinically mimic more common benign der-
matoses such as eczema, psoriasis, and drug eruptions.5-10 As
the malignancy advances, involvement of local and distal
lymph nodes, blood, and other visceral organs may occur,
and outcomes can be devastating.
Notably, epidemiologic studies reported nonrandom distri-
bution of patients with CTCL in different parts of the world,
including Sweden,11 Pittsburgh,12 and Texas.13,14 This cancer
was reported to occur in married couples and cluster in
families.15 The nonrandom distribution of patients with CTCL
suggests that external and potentially preventable risk factors
may exist for this malignancy. While several agents such as
hydrochlorothiazide diuretics as well as some bacterial and
viral agents were implicated as possible triggers of CTCL, the
precise nature of this cancer initiator(s)/promoter(s) remains
largely unknown.16
We recently published for the first time a comprehensive
investigation on CTCL epidemiology in Canada, which illus-
trated trends that were similar to the ones observed in the
United States and also identified nonrandom geographic clus-
tering for this malignancy in our country.17 The incidence
rates of all CTCL types in Canada were on the rise during
1992 to 1998 and then stabilized at 11.32 cases per 1 million
individuals per year (95% confidence interval [CI], 11.05-
11.59), consistent with the US rate of ~10.2 cases per 1 mil-
lion population per year.18 Patients’ clinical characteristics
(eg, mean age of ~59.4 years at the time of diagnosis and male
disease predominance) were also confirmed by this study.
Notably, the geographic analysis of CTCL distribution
across the Canadian provinces revealed nonuniform distribu-
tion across the country, where Newfoundland and Labrador,
Nova Scotia, New Brunswick, Manitoba, and Saskatchewan
had higher incidence rates than the average rate in Canada,
while Ontario had the lowest incidence rate for CTCL.
Furthermore, these trends were also consistent at the city
level, where Moncton, St John’s, Saint John, Winnipeg, and
Regina displayed the highest incidence rates of CTCL in
Canada, while Ontario/Québec administrative cities, includ-
ing Ottawa, Gatineau, and Québec City, reported signifi-
cantly lower disease rates. Analysis of incidence rates by
postal codes (forward sortation areas or FSAs) identified
several regions with considerably high CTCL incidence.
These FSAs in many cases were covering industrial regions
in Canadian cities. In contrast, Ottawa (the city with minimal
industrial presence) contained 3 of 8 in the country statisti-
cally significant populous FSAs with zero CTCL incidence.
In the initial study describing this data set, we have pub-
lished only the statistically significant findings,17 which
excluded a significant amount of data that may be helpful to
practicing dermatologists across Canada. In the present
report, we provide all the collected data on CTCL patient
incidence in Canada during 1992 to 2010.
Methods
Methods in the current study are identical to the methods
described in our previous publication.17 Briefly, we exam-
ined the data on CTCL incidence using 2 distinct population-
based cancer databases, Canadian Cancer Registry (CCR)
and Le Registre Québécois du Cancer (LRQC), for the period
of 1992 to 2010 using the third edition of the International
Classification of Diseases for Oncology (ICD-O-3) codes for
10 CTCL subtypes, as previously reported.17 To conduct this
research, a research ethics board waiver was obtained from
McGill University Health Centre. We interpreted and pre-
sented the data on patient reporting province, city, and FSA
(geographical region where postal codes start with the same
3 characters) as previously described.17
Ghazawi et al 3

Mandatory Data Rounding

A number of confidentiality rules apply to CCR and LRQC
data prior to their publication, such as random rounding of
variables as absolute numbers for CTCL cases; these are
indicated whenever actual case numbers are presented in
tables. In regards to random rounding of tabular data, the
Social Sciences and Humanities Research Council (SSHRC)/
Statistics Canada requires to round each cell count, indepen-
dently of other cells, to a lower or higher multiple of 5 using
an unbiased random rounding scheme where counts are more
likely to be rounded to their nearest multiple of 5. No number
≥1 and <5 cases can be released, as per the SSHRC regula-
tion to protect patient confidentiality. We were able to review
and report communities where zero CTCL cases were docu-
mented. The raw data were used for a number of analyses (as
indicated) in the study.

Statistical and Mapping Analyses

Statistical analysis was performed as previously discussed.17
Unless otherwise specified, analysis of the complete data on
all patients with CTCL across Canada for the period 1992 to
2010 is presented throughout the article. Incidence rates and,
for a subset of data, 95% CIs were calculated and reported
overall and for specific regions that were identified by the
mapping analysis. Unless otherwise specified, 1996, 2001,
2006, and 2011 Canadian Census data were used for all pop-
ulation analyses.
Geographic maps of Canada, which are divided per FSA
codes indicating the residence of patients with CTCL
recorded by the CCR and LRQC databases, were generated
using geographic information systems software (ArcMap
10.4 from Environmental Systems Research Institute [ESRI],
Redlands, California). In mapping of the CCR and LRQC
results, only FSAs with populations of at least >5000 indi-
viduals based on 1996, 2001, 2006, and 2001 census data
were selected to reduce erroneous false-positive hits, where
a single case of CTCL occurring within a scarcely populated
(<5000 residents) FSA might have artificially inflated the
incidence rate.
Results
As previously discussed,17 we analyzed 6685 patients with
CTCL who were identified in Canada during 1992 to 2010
(Figure 1). The incidence rates for the specific subtypes of
CTCL are summarized in Figure 2. Mycosis fungoides inci-
dence rate was ~4 cases per million per year, and this rate
decreased slightly over time (Figure 2). Several other sub-
types of CTCL displayed a steady increase in incidence,
including Sézary syndrome, extranodal natural killer (NK)/
T-cell lymphoma (nasal type), mature T-cell lymphoma (not
otherwise specified [NOS]), angioimmunoblastic T-cell
lymphoma, and adult T-cell leukemia/lymphoma subtypes
Figure 1.  Predominance of different cutaneous T-cell lymphoma
(CTCL) subtypes in the Canadian population during 1992 to
2010: mycosis fungoides (MF; 37.5%); Sézary syndrome (SS; 1.6%);
mature T-cell lymphoma not otherwise specified (MTCL; 17%);
angioimmunoblastic T-cell lymphoma (AITL; 6%); subcutaneous
panniculitis-like T-cell lymphoma (SPTCL; 0.6%), CTCL not
otherwise specified (CTCL NOS; 8.5%); CD-30+ anaplastic
large-cell lymphoma, both T-cell and null-cell type (CD30+ ALCL;
19.5%); primary CD-30+ lymphoproliferative disorders (PCLPD;
2.5%); extranodal natural killer (NK)/T-cell lymphoma, nasal type
(ENKL; 3.7%); and adult T-cell leukemia/lymphoma (ATLL; 3%).
This figure was developed based on the data from our previous
report.17
(Figure 2). In addition, the rate of the CTCL NOS variant
declined steadily over time, indicating a rise in specific sub-
type reporting for CTCL during 1992 to 2010.
As discussed in the initial publication,17 analysis of patient
distribution and incidence rates revealed that the eastern
provinces of Newfoundland and Labrador, Nova Scotia, and
New Brunswick, as well as the prairie provinces of Manitoba
and Saskatchewan, had significantly elevated CTCL inci-
dence rates (Figure 3). This was also confirmed by the analy-
sis on the city level, where Saint John, Moncton, St John’s,
Regina, and Winnipeg have displayed higher incidence rates
of disease compared to the rest of Canada. On the other hand,
several cities in Ontario (eg, Kingston, Brampton, and
Toronto) and Québec (Québec City, Beauport, Saguenay, and
Saint-Jean-sur-Richelieu) had lower incidence rates of CTCL
than the national average. Notably, the city of Ottawa, the
national capital, had the lowest CTCL incidence rate of all
major Canadian cities at 4.04 (95% CI, 3.11-5.14) cases per
million per year. Similarly, the adjacent city of Gatineau,
Québec, had a significantly lower incidence rate of 6.22
4 Journal of Cutaneous Medicine and Surgery 00(0)

Figure 2.  Changing incidence rates (cases per 1 million individuals per year) for each cutaneous T-cell lymphoma (CTCL) subtype
during 1992 to 2010. Analysis of the CTCL subtype incidence rates over time is shown for the 10 subtypes of CTCL. This figure was
developed based on the data from our previous report.17 For definitions of abbreviations, see Figure 1.
Ghazawi et al 5
Figure 3.  Incidence rates of cutaneous T-cell lymphoma (CTCL) (per 1 million individuals per year) in the Canadian provinces during
1992 to 2010. *statistically significant lower incidence rate (P < .05) compared to Canada. **Statistically significant higher incidence rates
(P < .05) compared to Canada. This figure was developed based on the data from our previous report.17
(95% CI, 4.20-8.88) cases per million per year. Complete
information on CTCL incidence rates for all major Canadian
cities is provided in Table 1.
Our previous analysis by FSAs (regions where all postal
codes start with the same 3 characters) identified select
regions in the country where several high-incidence FSAs
were adjacent. Furthermore, in a number of instances, we
observed an important additional clustering of patients within
the identified FSAs, where CTCL cases were not occurring in
a random, “buckshot” distribution but clustered in specific
regions within each high-incidence FSA. At that time, only
the statistically significant FSAs were reported.17 However,
we believe it is important to provide incidence data for all
analyzed FSAs to the Canadian practitioners (Suppl. Table
S1). Mapping geographically all FSAs that had ≥2-fold higher
incidence of CTCL further strengthens the clustering trends
that were identified in our previous report.17 FSAs with an
increased incidence of CTCL are geographically depicted in
different shades of brown (depending on the fold increase in
incidence rate) in Figure 4. Notably, many of these FSAs
were contiguous as in Newfoundland and Labrador (A0C,
A0H, and A0J; A1A, A1C, A1L, and A1M), New Brunswick
(E4P and E4K), Québec (H9S and H4W), Manitoba (R3B
and R3C), and British Columbia (V9K and V9P, V7S and
V7R, and V6L and V6M).
Similarly, we also conducted an incidence rate analysis to
identify areas that were spared (ie, zero cases) by CTCL dur-
ing 1992 to 2010. In our study, 8 FSAs were reported as sta-
tistically significant, and most (6/8) were in Ontario.17 Here
we present all the FSAs with the population of ≥10 000 resi-
dents that had zero cases of this skin lymphoma during 1992
to 2010 (Table 2). Consistent with our previously reported
trends, 11 of 22 of these communities were in Ontario, the
province with the lowest CTCL incidence rate; 6 of 22 were
in Québec; and 3 of 22 were in Alberta. As previously
highlighted,17 3 of the zero-incidence FSAs clustered in
Ottawa, the nation’s capital and main administrative city.
In our previous analysis of the distribution of patients
with CTCL in Canada,17 we noted that in several cases, as
described for the cities of Montréal, Hamilton, Oakville, and
Winnipeg, statistically significant high-incidence FSAs were
located in industrial regions of these cities and/or near impor-
tant transportation junctions. Furthermore, in several other
instances such as in the town of Englehart, Ontario, patients
with this rare cancer were residing in a proximity of major
railway stations and transportation ports.17 In this analysis,
we extend our findings and correlate distribution of high-
incidence FSAs near important seaports. As noted for the cit-
ies of Charlottetown in Prince Edward Island, Halifax in
Nova Scotia, Gaspé in Quebec, Hamilton in Ontario, and
Vancouver/Vancouver Island in British Columbia, the high-
lighted high-incidence FSAs were located in close proximity
(or overlapping) with marine or ferry terminals (Suppl.
Figure S1).
Discussion
In this report, we provided complete data on CTCL incidence
across Canada and reported important trends that further
strengthen our earlier presented statistically significant clus-
tering findings.17 We presented a detailed account of CTCL
incidence on the provincial, city, and FSA levels and high-
lighted concordant trends, where provinces with a high inci-
dence of CTCL had a higher incidence of CTCL in their major
cities and accounted for a significant number of high-incidence
FSAs. In many cases, these FSAs clustered together and
painted important major industrial areas in these cities. We
also highlight that in a number of instances, these high-inci-
dence FSAs were located near seaports and transportation
junctions.
6 Journal of Cutaneous Medicine and Surgery 00(0)

Table 1.  Incidence of Cutaneous T-Cell Lymphoma (CTCL) in Table 1. (continued)

Canadian Cities.a
Incidence
Incidence per 1 000 000
per 1 000 000 Average Individuals
Average Individuals City Casesb Populationc per Yeard
City Casesb Populationc per Yeard
  St Albert 10 60 000 9
High-incidence Canadian cities  Coquitlam 20 121 000 9
  Saint John 35 69 000 27  Sherbrooke 25 151 000 9
 Moncton 30 67 000 24  Kitchener 35 212 000 9
  Medicine Hat 20 59 000 18  Cambridge 20 124 000 9
  St John’s 35 103 000 18   New Westminster 10 62 000 8
 Victoria 25 79 000 17   Norfolk County 10 63 000 8
 Lethbridge 25 79 000 17   Greater Sudbury 25 159 000 8
 Regina 55 186 000 16  Calgary 160 1 043 000 8
 Saint-Hyacinthe 15 52 000 15  Mississauga 105 691 000 8
  Maple Ridge 20 73 000 15  Longueuil 35 230 000 8
 LaSalle 20 73 000 14  Ajax 15 100 000 8
 Brantford 25 92 000 14 Low-incidence Canadian cities
 Winnipeg 175 649 000 14  Markham 40 282 000 7
 Burlington 45 170 000 14  London 50 359 000 7
 Saskatoon 55 212 000 14  Beauport 10 73 000 7
 Oakville 45 174 000 14  York 20 147 000 7
Average-incidence Canadian cities  Saint-Laurent 10 76 000 7
 Delta 25 98 000 13  Quebec 65 504 000 7
  Cape Breton 25 100 000 13  Whitby 15 117 000 7
 Granby 15 61 000 13  Toronto 320 2 559 000 7
 Chicoutimi 15 62 000 13  Kingston 15 120 000 7
 Vancouver 140 591 000 12  Kamloops 10 83 000 6
  Thunder Bay 25 109 000 12  Gatineau 30 254 000 6
  St Catharines 30 132 000 12  Vaughan 30 264 000 6
 Kelowna 25 112 000 12  Pickering 10 88 000 6
 Richmond 40 182 000 12  Saint-Jean-sur- 10 90 000 6
 Guelph 25 118 000 11 Richelieu
 Halifax 80 381 000 11  Saguenay 15 144 000 5
 Laval 80 385 000 11  Brampton 45 479 000 5
 Hamilton 105 512 000 11   East York 10 108 000 5
 Waterloo 20 98 000 11   Richmond Hill 15 174 000 5
 Langley 20 99 000 11   North York 50 590 000 4
 Edmonton 155 771 000 11  Scarborough 45 559 000 4
  Sault Ste. Marie 15 75 000 11  Ottawa 65 848 000 4
 Abbotsford 25 129 000 10 a
Cities are divided into high incidence, average incidence, and low
 Burnaby 40 213 000 10
incidence compared to the average CTCL incidence rate in Canada (11.32
 Fredericton 10 53 000 10 cases per 1 million individuals per year).
 Windsor 40 214 000 10 b
All case numbers are rounded to the nearest 5.
c
  North Bay 10 54 000 10 All population numbers are rounded to the nearest thousand.
d
 Surrey 80 432 000 10 All incidence rates are rounded to nearest whole number.
 Nanaimo 15 81 000 10
  Stoney Creek 10 54 000 10 Importantly, environmental effects of seaports as signifi-
 Montreal 300 1 635 000 10 cant sources of pollution and their association with carcino-
 Saanich 20 109 000 10
genesis were highlighted in a number of studies.19,20 In fact,
  Niagara Falls 15 83 000 10
many pollutants can be released in the ports from ships that
  North Vancouver 15 83 000 9
operate on low-grade fuels, during the dredging process, and
  Red Deer 15 87 000 9
from spillage of cargo material (including chemicals, fuel
 Oshawa 25 146 000 9
  Strathcona County 15 88 000 9
products, and heavy metals) during loading. Furthermore, it
has been established that incomplete combustion of diesel
(continued) fuels by large ships releases many pollutants in significant
Ghazawi et al 7

Figure 4. (continued)
8 Journal of Cutaneous Medicine and Surgery 00(0)

Figure 4. (continued)
Ghazawi et al 9

Figure 4.  Geographic maps illustrating case clustering (low-incidence and high-incidence rates) by forward sortation area (FSA: the first
3 letters and numbers in the postal code). High-incidence FSAs are highlighted in different shades of brown, and low-incidence FSAs are
highlighted in gray. Data are presented in 19 maps (A-S) showing different regions of Canada.
10 Journal of Cutaneous Medicine and Surgery 00(0)

Table 2.  List of Populous Forward Sortation Areas (FSAs) in Canada With Zero Incidence of Cutaneous T-Cell Lymphoma During
1992 to 2010.

Incidence per 1,000,000 Individuals

FSA Description Average Populationa per Year From 1992 to 2010
B6L Nova Scotia 13 000 0
J2W Québec 23 000 0
J5M Québec 16 000 0
J5K Québec 12 000 0
J5T Québec 13 000 0
G4T Québec 13 000 0
G9H Québec 11 000 0
K1G Ontario 34 000 0
K2K Ontario 19 000 0
K2S Ontario 17 000 0
L4R Ontario 18 000 0
L4S Ontario 24 000 0
L9M Ontario 13 000 0
M9M Ontario 20 000 0
M5S Ontario 13 000 0
N3W Ontario 13 000 0
N7A Ontario 12 000 0
L9Z Ontario 16 000 0
T5Y Alberta 25 000 0
T4V Alberta 17 000 0
T4T Alberta 14 000 0
V9Z British Columbia 16 000 0
a
All population numbers are rounded to the nearest thousand.

quantities such as carbon monoxide, sulfur oxides, nitrogen
oxides, volatile hydrocarbons, and low molecular weight
polyaromatic hydrocarbons, according to the US National
Toxicology Program.21 Indeed, such emissions from diesel
engines have been directly linked to a number of cancers,
including bladder cancer, leukemia, and non-Hodgkin lym-
phomas.22 Also, in many cases, major railroad lines and
highways connect to ports, thereby increasing traffic of haz-
ardous materials through a given area. The implication in
carcinogenesis of particulate matters in ambient air adjacent
to industrial regions, seaports, and major highways was eval-
uated in a number of studies. Specifically, in Hamilton,
Ontario, mice that were exposed to ambient air adjacent to
the industrial part of Hamilton, which includes steel mills, a
highway, and a seaport, were shown to develop many heri-
table mutations at repetitive DNA loci.23,24 These mutations
were not observed in similar mice that were reared 30 km
away in rural Ontario or in mice housed in the same facilities
but whose surrounding air was purified by a high-efficiency
particulate air (HEPA) filtration system. Therefore, it is pos-
sible that ambient pollutant air exposure from one or more
sources can be directly implicated in lymphomagenesis. It is
likely, however, that a combination of several factors, includ-
ing environmental exposures, among others, may increase a
person’s chance of developing CTCL, and it is important to
investigate the identity of such factors.
Importantly, this nonrandom distribution of CTCL cases
does not appear to be correlated to the high density of derma-
tologists in a given province as many of the provinces with
high CTCL incidence have very few dermatologists. In fact,
the CTCL incidence rates in the provinces of Ontario and
Québec, where more than 65% of the Canadian dermatologist
workforce is concentrated, were relatively low compared to
the rest of Canada. Similarly, there appears to be no correlation
between the presence of multidisciplinary specialized CTCL
clinics, which are available in Ottawa, Toronto, Québec City,
Montréal, Calgary, Edmonton, and Vancouver, and increased
incidence of CTCL cases in these cities. In fact, to our knowl-
edge, such specialized clinics are not yet organized in New
Brunswick, Newfoundland and Labrador, Saskatchewan, or
Manitoba, where an unusually high incidence of CTCL was
observed. These data bring to the forefront the need to redis-
tribute available health care resources to ensure that patients
and physicians, who treat them, have adequate access to spe-
cialized diagnostic tools (eg, flow cytometry, immunopheno-
typing, T-cell receptor clonality analysis) and treatments (eg,
extracorporeal photophoresis, psoralen and ultraviolet A
[PUVA] therapy) in these cities. We must also ensure that indi-
viduals in these underserved communities have adequate edu-
cation and support resources to battle their skin lymphomas.
It is notable that the average age of CTCL diagnosis in
African American and Hispanic patients is significantly
Ghazawi et al 11
younger than in white individuals.25-29 Furthermore, African
American men typically present with a higher clinical stage
at the time of diagnosis and follow a more aggressive clinical
course.13,25,29 Unfortunately, we were not able to analyze data
on ethnic background of Canadian patients as the CCR/
LRQC databases do not provide/release these data.
Finally, parallels can be drawn in medicine and oncology
for other rare cancers, where, due to increased incidence in
certain populations and/or geographic areas, it was possible
to identify a definitive trigger. For instance, after studying
the prevalence of mesotheliomas in asbestos mines of South
Africa and in Québec, Canada, asbestos was established as a
critical factor responsible for this deadly disease. Similarly, a
study of a small arsenic mining town in Prussia in 1898,
where chronic poisoning took place through the use of con-
taminated drinking water, helped establish the link between
arsenic and the occurrence of arsenical keratoses and skin
squamous cell carcinomas. Therefore, it appears likely that
future epidemiologic studies that are similar to this one will
reveal regional clustering of patients and may lead to an
identification of environmental triggers for CTCL and poten-
tially other rare cancers.
Acknowledgments
We thank all the staff that administered the data registries included
in this analysis. The interpretation, analysis, and reporting of these
data are the sole responsibility of the authors.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
work was supported by the new investigator funding program from
the Ottawa Hospital Research Institute to Dr Litvinov and the
Canadian Dermatology Foundation research grants to Dr Sasseville
and Dr Litvinov, Joan Sealy Trust Cancer Research to Dr Litvinov,
and the Fonds de la recherche en santé du Québec (FRSQ) research
grant to Dr Sasseville (FRSQ 22648) and to Dr Litvinov (FRSQ
34753 and 36769).
ORCID iD
Steven Glassman http://orcid.org/0000-0002-9699-303X
Kevin Pehr http://orcid.org/0000-0002-2950-4603
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