Post Radiotherapy “Isolated LP of the Lips” in a Non-Hodgkin Lymphoma Patient: A Possible Relation

doi:10.4236/jcdsa.2012.23044

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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,

Khalid Bahamdan5

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.

Email: [email protected]

Received May 21st, 2012; revised June 30th, 2012; accepted July 12th, 2012

ABSTRACT

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

1. Introduction

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 [1]. Isolated LP of the lip is a

known condition which was first reported in 1995 [2].

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.

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.

3. Discussion

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

[3]. 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

[4], 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-

entation.

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 [6]. A

bipolar LP of gingiva and vulva has been described as

vulvovaginal-gingival LP syndrome [7] in which other

mucosae may be involved as well. In 1% of patient popu-

lation, esophagus is the only site involved with LP [8],

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

Post Radiotherapy “Isolated LP of the Lips” in a Non-Hodgkin Lymphoma Patient: A Possible Relation

236

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 [9], but in

monitoring the disease OLP activity serum IL-8 level

was found more sensitive marker than serum IL-6 [10].

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 [11]. 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

[12], 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 [13]. 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 [17]. 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

[25]. 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 [26]. 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!

4. Conclusion

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

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

in between the sharp angles (Diagram 1).

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