Journal of Cosmetics, Dermatological Sciences and Applications, 2012, 2, 234-238
http://dx.doi.org/10.4236/jcdsa.2012.23044 Published Online September 2012 (http://www.SciRP.org/journal/jcdsa)
Post Radiotherapy “Isolated LP of the Lips” in a
Non-Hodgkin Lymphoma Patient: A Possible Relation
Hamdi H. Shelleh1, Husni S. Al Hateeti2, Hamad A. Al Fahhad3, Sarosh A. Khan4, Latif A. Khan2,
1Dermatology Department, Nagran General Hospital, Najran, KSA; 2Hematology, MRCP, London, UK; 3Dermatology, Najran Uni-
versity, Najran, KSA; 4Medicine, On-Line Physician Academy, Sirangar, India; 5Dermatology, King Khalid University, Abha, KSA.
Received May 21st, 2012; revised June 30th, 2012; accepted July 12th, 2012
We report upon a case of 62 years old Saudi male with non-Hodgkin lymphoma who developed lichen planus (LP) on
the inner aspect of the upper lip six months after finishing radiotherapy. The diagnosis of LP was confirmed by histo-
pathology. Literature review reveals few countable similar reports of “post radiotherapyoral LP (OLP)”. However, the
isolated location of lichen planus on the upper lip per se in this case merits reporting being exceptional and reported
before as isolated lichen planus of the lips (ILPL). We assume, after screening literature, that this is the first report of
post radiotherapy ILPL in Arabian Gulf countries, though it may be underestimated and underreported. The etiological
relation between radiotherapy and LP is discussed.
Keywords: LP; OLP; Isolated Lichen Planus of the Lip; ILPL; Lymphoma; Radiotherapy Induced LP
OLP is a chronic T-cell mediated inflammatory disease
of the oral mucosa of unknown etiology which rarely un-
dergoes spontaneous remission; rather, it has the poten-
tial to become malignant . Isolated LP of the lip is a
known condition which was first reported in 1995 .
Several reports succeeded, in which the lower lip was the
mostly involved site, but in some the upper lip was. This
condition may be underestimated and therefore under-
reported in medical literature. This may explain the scar-
city of this entity in literature, and justify reporting it
from this region.
2. Case Report
A 62 years old Saudi male (Figure 1), attended skin
OPD with black ulcerative lesion on the oral aspects of
upper lip since 4 months. The lesion was painful while
eating especially when ulcerations existed. He was mar-
kedly anxious for his lesion as he had had a past history
of lymphoma and was scared of a possible linkage be-
tween both. He was not on drugs and had no other skin
lesions elsewhere. Likewise, he was not a smoker, and
denied any tobacco chewing. The history of lymphoma
started since March 1999 as a submandibular enlarged
lymphnode with general body aches, fever, decreased
appetite, and rapid weight loss. The patient was referred
to King Faisal Specialist Hospital (KFSH), Riyadh, where
he was examined, biopsied and diagnosed as “grade I
follicular small cell non Hodgkin lymphoma” according
to the final report given to him. Aspirate of bone marrow
was positive for malignant cell suggesting the dissemina-
tion the disease. This was confirmed by emittion tomo-
graphy scanning which proved positive in submandibular
region, sternum, ribs, lumber spine V and sacral I. On an-
other visit in April 2001 there was progression of the dis-
ease in the mediastinum. On December 2001 he presented
with a new painful swelling on the right scapular region
Figure 1. Superficial ulcerations on reticulate hyperpig-
mented erythematous ill defined surface limited to the inner
aspect of upper lip.
Copyright © 2012 SciRes. JCDSA
Post Radiotherapy “Isolated LP of the Lips” in a Non-Hodgkin Lymphoma Patient: A Possible Relation 235
which proved on CT to be a mass in the deltoid muscle
with bone changes in the acromial head. There was ab-
dominal lymphadenopathy as well. A new fine needle
aspiration revealed AB lymphoid cells and large follicu-
lar simple cells. The scenario of treatment was decided to
be a combination of radio-chemotherapy for 6 therapy
cycles. Accepting that, he went on with the treatment
after which he markedly improved. The entire body hair
fell down, but restored again after 6 months of therapy.
He was on regular follow-up at the oncology centre for
10 months. The current clinical examination at the der-
matology clinic revealed diffuse lattice-like whitish le-
sion on hyperpigmented flat surface occupying the entire
inner aspect of the upper lip with few superficial ulcera-
tions. The lesion was not infiltrated; there were no en-
larged submandibular lymphnodes. The upper anterior
gingiva had a furry appearance with whitish discoloration.
The rest of the oral cavity was thoroughly intact and so
were the skin and skin appendages elsewhere. The histo-
pathological examination of the lip revealed an epidermis
with hyperkeratosis and acanthosis, the upper dermis was
occupied with a dense band of lymphocytic infiltrate
along the epidermal-dermal junction, suggesting the di-
agnosis of lichen planus. Atypical cells of any type could
not be found. Routine laboratory investigations revealed:
WBC: 6540/mm (seg. 31.7%, mono. 6.7%, eosinocytes.
1.7%, and lymphocytes 59.8%), ESR: 6 mm/1st h. No
other reports of significance. Liver Function Tests were
within normal limits, and so were the hepatic viral markers.
Oral lichen planus is a relatively frequent inflammatory
mucocutaneous disease of middle-aged patients, affect-
ing approximately 1.27% of the world population. The
association with other immune diseases and the damage
to the basal keratinocytes in lichen planus supports an
autoimmune aetiology mediated by autocytotoxic T-cells.
This case of OLP is of the erosive form. OLP in this case
is confined to the upper lip. We think that the special lo-
cation aforementioned and the special timing; six months
after cessation of lymphoma radiotherapy make it worth
reporting. The patient was anxious for his oral lesion mi-
ght be a recurrence of lymphoma, and we were, on our
side, anxious too; whether his oral LP could be radio-
therapy induced condition. Nevertheless, dermatology is
a branch of terminology; let aside the relation of LP with
malignancy and radiotherapy which need further studies
to settle, this case has special dermatological significance
in terms of the location exclusively on the oral mucosa
—hence called oral LP in isolation—and the allocation
merely on the inner aspect of upper lip—called isolated
lichen planus of the lips. Thus, it is sub type of sub-type
of LP. However, we do not get engaged a lot in such di-
visions and subdivisions till proved significant, as LP at
last is LP, apart from such distribution and localization.
Oral involvement occurs as part of LP disease in 50% of
LP patient population, even 60% - 70% in another study
. It may precede, accompany or follow lesions else-
where on the skin in the context of LP disease. “OLP in
isolation” occurs in 20% - 30% of the patient population
, it affects 1% - 2% of population in general and has
the same histopathology of cutaneous LP. It may develop
on any site of the oral mucosa and usually asymptomatic
except for the atrophic and erosive patterns which may
cause burning sensation and trouble eating. For easier
clinical approach, OLP may take diverse patterns or pre-
sentations which include [3,5]: 1) The reticular pattern: it
is the most common pattern of OLP, it is presented as
reticulated white papular streaks; 2) The papular pattern:
usually seen together mixing within the reticulate pattern;
3) The plaque pattern: resembles leukoplakia, the border
of the plaque is reticulate as in type1; 4) The atrophic
pattern: also the border is reticulate here; 5) The bullous
LP is rarely encountered; 6) The desquamative gingivitis;
7) The gingival stomatitis; 8) Erosive/ulcerative LP: this
predominates in the elderly, but it is comparatively un-
common pattern. Ulcers develop secondary to atrophic
lesion or blisters, they are irregular shaped with slough,
but the red halo and whitish striae are pathognomonic of
oral LP. Our patient belongs to this type of clinical pres-
Though any of these types may occur alone, the clini-
cal picture may be a mixture of more than one. Location
wise, the buccal “gingival and glossal” mucosae are the
most commonly affected sites. But the palate, floor of
month, lips and any area of the oral cavity may also be
affected. LP of the lips usually has oral lesions elsewhere,
but when in isolation they are reported as ILPL . A
bipolar LP of gingiva and vulva has been described as
vulvovaginal-gingival LP syndrome  in which other
mucosae may be involved as well. In 1% of patient popu-
lation, esophagus is the only site involved with LP ,
this represents a singular mucosal involvement of OLP as
on the lip, and similar to the singular involvement of the
glans or vulva. Again it is not known why a small par-
ticular area of mucosa or skin only reacts with a disease
which is supposed to be of a systemic immunological
mechanism in the absence of localizing factors like ra-
diotherapy or other irritating and mediating factors. For
instance, OLP may occur adjacent to gold, mercury and
other amalgam dental fillings. This assumes a role of
these elements in the pathogenesis of localized LP. How-
ever, our patient has not been using any of the suspected
drugs, and had no close adjuvant dental fillings to be in-
criminated, whereas, radiotherapy was the only preced-
ing condition to presume a potential correlation. Consid-
erable evidence now exist that the etiological process
Copyright © 2012 SciRes. JCDSA
Post Radiotherapy “Isolated LP of the Lips” in a Non-Hodgkin Lymphoma Patient: A Possible Relation
underlying LP is auto-immune mediated. Langerhans cells
increase in the early lesion of LP, and the dermal infil-
trate consists largely of T-cells, 40% of these T-cells in
the dermal epidermal junction and 80% in the dermis are
of helper/inducer subset (CD4+). The T-cells represent
an antigen-stimulated cell. This antigen, whether it be a
virus or drug carried on the cell surface, could alter the
T-cell interpretation of the histocompatibility complex so
that it recognizes it as foreign and attacks it. A constant
feature of the lymphocytes in lichenoid reactions is their
epidermotropism; the affinity for the epidermis. Adjacent
keratinocytes produce a series of cytokines that play a
critical role in attracting lymphocytes within the epider-
mis. The keratinocyte-lymphocyte interaction is impor-
tant in the pathogenesis of Lichenoid reactions. In the
primary phase of OLP IL-12 may drive the pathological
destruction in OLP lesions by elevating IFN-gamma pro-
tein locally. IFN-gamma may play an important role for
the pathological destruction in OLP lesions , but in
monitoring the disease OLP activity serum IL-8 level
was found more sensitive marker than serum IL-6 .
However, serum and salivary IL-18 are elevated as well
correlating with the severity of illness. This may improve
the predictive or prognostic values of inflammatory cy-
tokines for OLP . Though it is an idiopathic disease a
relation to a chronic liver disease or immunodeficiency
has been proposed. The association of erosive LP with
primary biliary cirrhosis and chronic active hepatitismay
be related to an associated immunological pathogenesis
, or else, to an iatrogenic cause, as some patients
have received penicillamine therapy which was reported
as a triggering factor of LP. Hepatitis C virus infection
was reported in significant ratio of LP as well . This
puts a task on oral physicians and dentists to pay special
attention in any OLP lesion, and perform laboratory
screening to rule out these possible associations. An in-
creased incidence of glucose tolerance test in LP has
been reported. Lichen planus may be induced by neopla-
sia; paraneoplastic LP, and a cell-mediated immune reac-
tion possibly backs this association. It was reported with
thymoma, autoimmune diseases and Castleman’s tumor
[14-16]. After tumor resection LP lesions regressed and
melanosed. It is recommend that with patients presenting
a severe, therapy- resistant, erosive stomatitis, one should
be alert to the possibility of underlying immunological
diseases and/or tumors . OLP per se carries prema-
lignant potential, and a significant ratio of it may trans-
form to malignancy over years [1,18]. Similar to this case,
Sporadic cases of generalized or localized post radiothe-
rapy LP have been reported, being treated for different
types of cancers, but little is known about the mechanism.
[19-24]. We assume that LP-radiotherapy relation in these
patient is not fortuitous, OLP has developed as a result of
radiological trauma, besides the activation of T lympho-
cytes during carcinogenesis and/or radiation thru an auto-
immune mechanism. The isomorphic; or the “isoradio-
topic” response of skin to radiological trauma (Koebner’s
phenomenon) may issue as mucositis—the most common
complications of radiotherapy [20,23,24]. Mucositis me-
diates the pathogenic process and forms an inflammatory
basis for OLP. In addition to this, lymphocytes of CD8+
and CD4+ type become over sensitized to tumor antigens
of lymphoma cells, and/or get altered by frequent expo-
sure to radiotherapy, a condition of dysimmuno-reactivi-
ty or immuno-discrepancy ensues which bring about the
intrinsic production of various autoantibodies. These at-
tack the cross-reacting antigenic structures in the skin and/
or mucosae in an autoimmune process to produce the
clinical picture of LP or OLP causing cellular degenera-
tion, apoptosis and disruption of the basal membrane.
But why on the upper lip in this patient? The upper lip
was the most neighbouring region that was directly and
mostly hit by radiation therapy causing a mucosal injury,
and indirectly, by the mucosal damage resulting via an
autoimmune mechanism. Hence, we think that lichen pla-
nus has windows, directly opened with both neoplasms
and radiotherapy here allowing the interplay of traumatic,
humoral and cell-mediated responses in LP pathogenesis
. We found, after screening literature, that this is the
first case report of OLP induced by radiotherapy in Saudi
Arabia and in the Arabian Gulf countries. As in cutane-
ous LP, there is no specific treatment for OLP. New oral
retinoids (Temarotene, Feurelinide) appear promising. To-
pical cyclosporine has equivocal value. New trials sup-
port a significant response of OLP to the topical immune-
modulator; tacrolimus . Levamisole increases cellu-
lar immunity in many autoimmune and inflammatory
diseases. There has been significant success with Leva-
misolemonotherapy, and dramatic response to levamisole
with low dose prednisolone [26,27]. However, regular
follow-up, including biopsy, is important especially in
resistant erosive OLP in order to early pick up any sus-
pected malignant transformation. Once our patient was
reassured, he was missed on follow up, and appeared
again, 5 years later; healthy, but still with OPL, still lim-
ited to the upper lip, and still without signs of transfor-
mation, or recurrence of lymphoma. It was a survive!
Thus, radiotherapy elicited OLP may becomea true entity,
that needs further studies for confirmation. It may be due
to 2 factors: 1) traumatic radiological mucositis which
may act as a Koebner’s sign; 2) and/or autoimmune me-
chanism resulting from the aberrant cancer cells and/or
radiotherapy mutilating effect. OLP may be of the ILPL
type if lips were more adjuvant to irradiation source. This
is the first case of ILPL reported from KSA and Arabian
Copyright © 2012 SciRes. JCDSA
Post Radiotherapy “Isolated LP of the Lips” in a Non-Hodgkin Lymphoma Patient: A Possible Relation 237
Diagram 1. Cancer-radiotherapy-lichen planus-triangle; the
key ward is possibly the T-lymphocyte which gets disrupted
in-between the sharp angles.
Gulf countries, but it may be underestimated and under
reported. Doctors should be aware that neoplasms and/or
radiotherapy for neoplasms may induce OLP and OLP
may transform, this mandates awareness by the radiolo-
gist to focus their radiation beam as far as possible far
from the mucosae; it is fragile and may get easily trapped
in LP. Further research is required to elucidate the inter-
relations in the cancer-radiotherapy-LP triangle; the key
ward is possibly the T lymphocyte which gets disrupted
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