 |
|
Lentigo Maligna With Spread Onto Oral Mucosa
George Kroumpouzos, MD, PhD;
E. William Frank, MD;
Maj John G. Albertini, MC, USA;
James M. Krivo, MD;
Michael L. Ramsey, MD;
William B. Tyler, MD;
Lisa M. Cohen, MD
Arch Dermatol. 2002;138:1216-1220.
ABSTRACT
| |
Background Lentigo maligna (LM) is a form of melanoma in situ most often seen in
white patients on sun-exposed areas, primarily the head and neck. Spread of
LM onto the conjunctiva has been reported. There have been no reports of LM
extending onto oral mucosa.
Observations We report 4 cases of LM in white women with contiguous spread from perioral
areas to oral mucosa. The locations of the primary lesions were the vermilion
of the lip, vermilion and perioral skin, cheek, and cutaneous aspect of the
lip. Three cases showed focal histopathologic evidence of invasion during
the course of the disease. The lesions ran a prolonged course characterized
by repeated recurrences after surgery. Three of the cases required a complicated
reconstruction after surgical excision. Mohs surgery with rush permanent (paraffin-embedded)
sections resulted in a long remission in 2 cases, while in 1 patient, treatment
with carbon dioxide laser was unsuccessful.
Conclusions In a perioral distribution, LM can spread onto oral mucosa. This clinical
presentation may cause significant long-term morbidity, as indicated by a
high recurrence rate and/or progression to invasive melanoma. The oral mucosa
should be examined in patients with atypical pigmented perioral lesions.
INTRODUCTION
LENTIGO MALIGNA (LM) is a type of melanoma in situ with unique clinical
and histopathologic features.1 It occurs almost
exclusively in whites and shows a slight female preponderance.2
Lentigo maligna usually presents as a poorly circumscribed, variably colored
patch on sun-exposed areas, primarily the head and neck. The cheek is the
most common site. The margins of LM are often difficult to evaluate as a result
of mottled pigmentation and a background of solar lentigines and chronic photodamage.2 Long-term cumulative UV radiation is the most widely
recognized risk factor for the development of LM.3-4
Lentigo maligna melanoma (LMM), the invasive form of LM, is the most
common subtype of malignant melanoma on the face.5
Lentigo maligna occurs less commonly on the trunk and extremities. Lesions
previously reported on the subungual area,6-7
fingers,8-9 toes,10
hand,11 foot,11
scrotum,12 penis,13
and oral mucosa14-15 would be
classified today as acral lentiginous melanoma or another histologic type.16-17 The conjunctiva may be involved when
LM on the eyelids and/or periorbital areas spreads onto conjunctival mucosa.18-20 A case of melanoma
in situ involving the oral mucosa, lips, and perioral skin was reported and
was believed to have spread from the oral mucosa to the perioral skin.21 One of us (L.M.C.) recently reported extension of
recurrent LM of the cheek onto buccal mucosa (case 3 in this series).22
Herein, we report 4 cases of LM with contiguous spread from perioral
skin and/or vermilion of the lip onto oral mucosa. To our knowledge, this
clinical presentation has not been previously reported. All patients experienced
significant morbidity. We review the complicated course and prognosis of these
patients and discuss treatment options and the challenge of permanent cure.
The clinical data and response to treatment in the cases studied are summarized
in Table 1.
|
|
|
|
Clinical Data and Response to Treatment in the Cases Studied*
|
|
|
REPORT OF CASES
CASE 1
Biopsy specimens of the primary and recurrent lesions (the latter shown
in Figure 1 and Figure 2) demonstrated LM. The recurrent lesions were treated with
carbon dioxide laser excision followed by peripheral vaporization. The buccal
mucosal specimen removed during the laser excision revealed extensive LMM
in vertical growth phase with an invasive desmoplastic component and positive
margins. Three months later, biopsy specimens from residual pigmented oral
lesions taken by repeat laser excision showed residual LM in the oral commissure.
|
|
|
|
Figure 1. Irregularly pigmented lesion from
case 1 on the left upper lip extending onto the labial mucosa.
|
|
|
|
|
|
|
Figure 2. A group of pigmented papules from
case 1 on the left midanterior buccal mucosa extending to the commissure.
|
|
|
CASE 2
Biopsy specimens of the primary lesion (Figure 3) revealed LM. The lesion was excised with a 5-mm margin
using rush permanent sections. The upper lip was repaired with a rhombic flap
and the lower lip, with an advancement flap. Two years later, 3 tan to brown
pigmented patches were noted on the right buccal mucosa and lower labial mucosa
(Figure 4). Biopsy specimens confirmed
recurrent LM. Negative margins were obtained after 3 stages of excision with
rush permanent sections, and the defect was repaired with a full-thickness
skin graft from the groin. No recurrences or new atypical lesions have been
noted 5 years after excision.
|
|
|
|
Figure 3. A long-standing pigmented plaque
from case 2 involving the lips, right commissure, and perioral skin.
|
|
|
|
|
|
|
Figure 4. Tan to brown pigmented macules
from case 2 on the right midanterior buccal mucosa and lower labial mucosa.
|
|
|
CASE 3
A biopsy specimen of the primary lesion on the left cheek showed LM.
The lesion recurred several times and was excised after each recurrence; advancement
flap was used once for the repair. Ten years after the appearance of the primary
lesion, a recurrent lesion was noted on the left cheek and oral commissure.
This was treated with wide excision and reconstruction with a cervicofacial
rotation flap. Pathologic analysis showed a 3-mm-thick LMM, but the margins
were ambiguous. Three years later, extensive pigmentation was noted along
the scar from the previous cervicofacial flap that involved the advanced portions
of the flap and left oral commissure. The tumor extended onto the upper lip,
oral commissure, and buccal mucosa. All affected areas were excised using
rush permanent sections. The commissure was reconstructed with an intraoral
rotation flap, the lower lip with simple undermining and advancement, and
the cheek with a prefabricated supraclavicular flap. To date, there have been
no recurrences or new atypical lesions.
CASE 4
The primary lesion on the left upper lip extended onto the left oral
commissure, vermilion, and labial mucosa of the upper lip, and vermilion of
the lower lip. A biopsy specimen showed LM. The lesion was removed with narrow
margins, and the subsequent reconstruction used cheek advancement and lip
rotation flaps. Within the next 6 years, several recurrent lesions were noted
on the left upper lip and melolabial fold. For reconstruction, rotation flaps,
a cervicofacial myocutaneous platysma flap, and a myocutaneous orbicularis
flap were used. Two years later, a biopsy specimen of another recurrent lesion
on the left cheek and upper lip revealed a 0.43-mm-thick LMM. This was excised
with a 1-cm margin; a large cheek rotation flap was used for reconstruction.
The biopsy specimen showed negative margins. Recently, another recurrent lesion
on the left cheek and upper lip was excised twice with positive margins.
HISTOPATHOLOGIC FINDINGS
All biopsy specimens from LM lesions revealed similar histopathologic
features. Microscopic examination from a recurrent lesion from case 4 revealed
an atypical intraepidermal melanocytic proliferation over a scar (Figure 5). The pleomorphic melanocytes were
arranged as single units and small nests along the dermoepidermal junction.
In some areas, there was elongation of the rete ridges, whereas in others,
there was epidermal atrophy. Solar elastosis was noted. The atypical cells
showed hyperchromatic, enlarged, irregular nuclei and areas of pagetoid spread.
|
|
|
|
Figure 5. Biopsy specimen taken from a recurrent
lesion in case 4 demonstrates pleomorphic melanocytes with large, irregular
hyperchromatic nuclei and areas of pagetoid spread (original magnification
x200).
|
|
|
Biopsy specimens from the oral mucosal lesions of case 3 showed a proliferation
of solitary, pleomorphic melanocytes with hyperchromatic nuclei along the
basal and suprabasal layers (Figure 6).
Biopsy specimens from one of the oral lesions of case 1 (shown in Figure 2) demonstrated confluent nests of
atypical melanocytes within the lower portion of the epithelium (Figure 7). Focal pagetoid spread was noted.
In another biopsy specimen from the buccal mucosa, a dermal spindle cell neoplasm
was identified extending from the intraepidermal component. Patchy inflammation
and numerous melanophages were seen in the papillary dermis. The lesion was
positive for S100, consistent with desmoplastic melanoma.
|
|
|
|
Figure 6. Biopsy specimen taken from the
oral lesion in case 3 shows a proliferation of pleomorphic melanocytes with
enlarged hyperchromatic nuclei along the basal layer with focal upward growth
(original magnification x400).
|
|
|
|
|
|
|
Figure 7. Biopsy specimen taken from one
of the oral lesions in case 1 (shown in Figure 2) demonstrates pleomorphic,
hyperchromatic melanocytes forming horizontal confluent nests within the lower
portion of the epithelium (original magnification x200).
|
|
|
COMMENT
Lentigo maligna occurs in white patients on sun-exposed areas, predominantly
the head and neck. Extension onto mucosal surfaces such as the conjunctiva
has been exceptional.18-20
Herein, we report 4 cases of LM with spread from perioral areas onto oral
mucosa.
All patients had cutaneous lesions for several years before development
of intraoral involvement. The lesions ran a chronic course complicated by
several recurrences after surgery. Two of the patients never achieved complete
remission, and all experienced significant long-term morbidity. Primary melanoma
of the oral cavity can be excluded in our patients primarily by history. Metastatic
melanoma from the skin to the oral cavity is extremely rare and can be ruled
out by the absence of advanced primary skin tumor. Benign pigmented lesions
such as melanocytic nevi, oral melanoacanthomas, and oral and labial melanotic
macules can be excluded by the atypical histopathologic features.
The skin lesions showed typical histopathologic features of LM2, 23 such as solitary and small nests of
atypical melanocytes along the basal layer of the epidermis and adnexal structures,
epidermal atrophy, and solar elastosis. Pagetoid spread, melanophages, and
a dermal lymphohistiocytic infiltrate were sometimes seen. The histopathologic
characteristics of the oral lesions were consistent with contiguous spread
of the tumor from perioral skin areas.
Histopathologic evidence of invasion (LMM) was seen in 3 of the 4 patients
at some point during their long course. While this is a small sample size,
this suggests a higher than previously hypothesized progression of LM to LMM.24 The lesions may have progressed to an invasive stage
because of prolonged radial growth phases secondary to incomplete cure after
each recurrence. It has been shown that the risk for LMM increases proportionately
with lesional diameter.25 Furthermore, LM may
have progressed to LMM in areas that were not visible to the patient, thus
being unnoticed for long periods of time. As seen in case 1, an invasive component
was diagnosed in an oral LM of which the patient was not aware. Although development
of invasive areas may occur slowly and gradually, there have been reports
of rapid progression to LMM despite careful clinical follow-up.26-27
The recurrence of LM has been attributed to several factors, including
migration of malignant melanocytes from adjacent epidermis or migration of
deep periadnexal melanocytes to the epidermal surface.1-2
Most authors believe that surgical excision is the treatment of choice, but
the optimal surgical management of LM is still being defined. The recurrence
rate with standard surgical excision (9%) is lower than that reported with
destructive methods (35%-55%).28-29
The failure rate of standard excision may be due to microscopic extension
of LM by as much as 1.5 to 3 cm beyond the clinical margins.30-31
In most cases presented herein, conventional surgery, even with wide margins,
failed to eradicate the tumor completely and caused significant disfigurement.
The advocates of Mohs micrographic surgery for LM argue that this technique
has a high cure rate, spares normal tissue, and allows examination of 100%
of surgical margins.32 However, the value of
frozen vs rush permanent sections is debatable.31-37
While some authors33 suggest that frozen sections
are sensitive and specific for the diagnosis of melanoma, others32
argue that frozen sections contain artifacts and are often difficult to interpret.
The use of rush permanent sections34-35
may eliminate these problems but carries the disadvantage that only 1 stage
per day can be performed. A recent study32
recommended that if only frozen sections are to be performed, the final stage
of surgery should be submitted for analysis of permanent sections prior to
closing the wound. This ensures complete removal of the tumor while requiring
only 2 to 3 mm of additional tissue. In this study, rush permanent sections
were performed in cases 2 and 3 with excellent results.
In summary, we report 4 cases of cutaneous LM with extension onto oral
mucosa. The significant morbidity associated with this clinical presentation
is highlighted by the numerous recurrences and, in many instances, the need
for major reconstruction with subsequent cosmetic disfigurement. This clinical
presentation requires a high index of suspicion by the clinician. Examination
of the oral mucosa should be performed in all patients with atypical pigmented
perioral lesions. Furthermore, patients with perioral LM require long-term
follow-up because there is a high probability of recurrence and/or progression
to LMM.
AUTHOR INFORMATION
Accepted for publication January 24, 2002.
Corresponding author and reprints: Lisa M. Cohen, MD, 320 Needham
St, Suite 200, Newton, MA 02464 (e-mail: lcohen{at}cohenderm.com).
From the Departments of Dermatology, Veterans Affairs Medical Center,
Brockton, Mass (Dr Kroumpouzos); Beth Israel Deaconess Medical Center, Harvard
Medical School (Dr Frank), and New England Medical Center, Tufts University
School of Medicine (Dr Cohen), Boston, Mass; Brooke Army Medical Center, Fort
Sam Houston, Tex (Dr Albertini); Departments of Dermatology (Dr Ramsey) and
Pathology (Dr Tyler), Geisinger Medical Center, Danville, Pa; and Cohen Dermatopathology
PC, Newton, Mass (Dr Cohen). Dr Krivo is in private practice in Franklin Square,
NY.
REFERENCES
| |
1. Cohen LM. Lentigo maligna and lentigo maligna melanoma. J Am Acad Dermatol. 1995;33:923-936.
FULL TEXT
|
ISI
| PUBMED
2. Cohen LM. What's new in lentigo maligna. Adv Dermatol. 1999;15:203-231.
3. Holman CDJ, Armstrong BK. Cutaneous malignant melanoma and indicators of total accumulated exposure
to the sun: an analysis separating histogenetic types. J Natl Cancer Inst. 1984;73:75-82.
4. Elwood JM, Gallagher RP, Worth AJ, Wood WS, Pearson JC. Etiological differences between subtypes of cutaneous malignant melanoma:
Western Canada melanoma study. J Natl Cancer Inst. 1987;78:37-44.
5. Newell GR, Sider JG, Bergfelt L, Kripke ML. Incidence of cutaneous melanoma in the United States by histology with
special reference to the face. Cancer Res. 1988;48:5036-5041.
FREE FULL TEXT
6. Runne U, Tritsch H. Subunguale Lentigo Maligna mit streifenförmiger Nagelpigmentierung:
diagnostik und operative Behandlung. Z Hautkr. 1978;53:899-904.
PUBMED
7. Clouse WE, Sanders LJ. Subungual lentigo maligna. Cutis. 1985;36:153-155.
PUBMED
8. Miescher G. Über melanotische Präcancerose. Oncologia. 1954;7:92-94.
PUBMED
9. Lupulescu A, Pinkus H, Birmingham DJ, Usndek HE, Posch JL. Lentigo maligna of the fingertip: clinical histologic, and ultrastructural
studies of two cases. Arch Dermatol. 1973;107:717-722.
FREE FULL TEXT
10. Morishima T, Ishikawa T, Endo M, Tsujiguchi Y. Pagetoid malignant melanoma and lentigo maligna melanoma of toe: a
study with the fluorescence method (Falck and Hillarp). Arch Dermatol Res. 1978;262:275-283.
PUBMED
11. Rippey JJ, Rippey E. Malignant melanoma with adjacent Hutchinson's melanotic freckle in
black Africans. Pathology. 1977;9:105-109.
PUBMED
12. Steigleder G-K. Pseudo-Paget des skrotums. Dermatologica. 1958;117:165-172.
PUBMED
13. Aronson PJ, Whitney DH, Soltani K, Medencia M. Cryosurgical treatment of dysplastic lentigo of the glans penis. J Dermatol Surg Oncol. 1984;10:60-62.
PUBMED
14. de Graciansky R, Mouly R, Timsit E, Guilaine J, Queran J, Larregue M. Dubreuilh's melanosis of the buccal mucosa. Bull Soc Fr Dermatol Syph. 1967;74:176-178.
PUBMED
15. Robinson L, Hukill PB. Hutchinson's melanotic freckle in oral mucous membrane. Cancer. 1970;26:297-302.
PUBMED
16. Arrington III JH, Reed RI, Ichinose H, Krementz ET. Plantar lentiginous melanoma: a distinctive variant of human cutaneous
melanoma. Am J Surg Pathol. 1977;1:131-143.
ISI
| PUBMED
17. Paladugu RR, Winberg CD, Yonemoto RH. Acral lentiginous melanoma: a clinicopathologic study of 36 patients. Cancer. 1983;52:161-168.
FULL TEXT
|
ISI
| PUBMED
18. Cohen LM, Zax RH. Recurrent lentigo maligna invading a skin graft successfully treated
with Mohs micrographic surgery. Cutis. 1996;57:175-178.
PUBMED
19. Hutchinson J. On tissue dotage. Arch Surg (London). 1892;3:315-322.
20. Hicks C, Liu C, Hiranandani M, Garner A, Hungerford J. Conjunctival melanoma after excision of a lentigo maligna melanoma
in the ipsilateral eyelid skin. Br J Ophthalmol. 1994;78:317-318.
FREE FULL TEXT
21. Horiuchi N, Tsunoda T, Suetake T, Kato T. Oral mucosa malignant melanoma in situ with involvement of the perioral
skin. Dermatology. 1994;188:66-68.
PUBMED
22. Cohen LM. Mohs surgery for lentigo maligna and melanoma. Facial Plast Surg Clin North Am. 1998;6:309-317.
23. Cohen LM. The starbust giant cell is useful for distinguishing lentigo maligna
from photodamaged skin. J Am Acad Dermatol. 1996;35:962-968.
FULL TEXT
|
ISI
| PUBMED
24. Weinstock MA, Sober AJ. The risk of progression of lentigo maligna to lentigo maligna melanoma. Br J Dermatol. 1987;116:303-310.
FULL TEXT
|
ISI
| PUBMED
25. Wayte DM, Helwig EB. Melanotic freckle of Hutchinson. Cancer. 1968;21:893-911.
FULL TEXT
|
ISI
| PUBMED
26. Michalik EE, Fitzpatrick TB, Sober AJ. Rapid progression of lentigo maligna to deeply invasive lentigo maligna
melanoma. Arch Dermatol. 1983;119:831-835.
FREE FULL TEXT
27. Kelly JW. Following lentigo maligna may not prevent the development of life-threatening
melanoma. Arch Dermatol. 1992;128:657-660.
FREE FULL TEXT
28. Pitman GH, Kopf AW, Bart RS, Gasson PR. Treatment of lentigo maligna and lentigo maligna melanoma. J Dermatol Surg Oncol. 1979;5:727-737.
PUBMED
29. Coleman 3rd WP, Davis RS, Reed RJ, Krementz ET. Treatment of lentigo maligna and lentigo maligna melanoma. J Dermatol Surg Oncol. 1980;6:476-479.
ISI
| PUBMED
30. Grande DJ, Koranda FC, Whitaker DC. Surgery of extensive, subclinical lentigo maligna. J Dermatol Surg Oncol. 1982;8:493-496.
PUBMED
31. Cohen LM, McCall MW, Hodge SJ, Freedman JD, Callen JP, Zax RH. Successful treatment of lentigo maligna and lentigo maligna melanoma
with Mohs micrographic surgery aided by rush permanent sections. Cancer. 1994;73:2964-2970.
FULL TEXT
|
ISI
| PUBMED
32. Cohen LM, McCall MW, Zax RH. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. Dermatol Surg. 1998;24:673-677.
FULL TEXT
|
ISI
| PUBMED
33. Zitelli JA. Mohs surgery for lentigo maligna [letter]. Arch Dermatol. 1991;127:1729.
FREE FULL TEXT
34. Dhawan SS, Wolf DJ, Rabinovitz HS, Poulos E. Lentigo maligna: the use of rush permanent sections in therapy. Arch Dermatol. 1990;126:928-930.
FREE FULL TEXT
35. Stonecipher MR, Leshin B, Patrick J, White WL. Management of lentigo maligna and lentigo maligna melanoma with paraffin-embedded
tangential sections: utility of immunoperoxidase staining and supplemental
vertical sections. J Am Acad Dermatol. 1993;29:589-594.
ISI
| PUBMED
36. Johnson TM, Headington JT, Baker SR, Lowe L. Usefulness of the staged excision for lentigo maligna and lentigo maligna
melanoma: the "square" procedure. J Am Acad Dermatol. 1997;37:758-764.
FULL TEXT
|
ISI
| PUBMED
37. Robinson JK. Margin control for lentigo maligna. J Am Acad Dermatol. 1994;31:79-85.
ISI
| PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Variation in the Diagnosis, Treatment, and Management of Melanoma In Situ: A Survey of US Dermatologists
Charles et al.
Arch Dermatol 2005;141:723-729.
ABSTRACT
| FULL TEXT
|
