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Research Letters |

Progression of Primary Acquired Melanosis With Atypia During Pregnancy FREE

Francesca Irvine, MBChB; Manjula Kumarasamy, FRCOphth; Ewan Kemp, FRCOphth; Fiona Roberts, FRCPath
[+] Author Affiliations

Author Affiliations: Department of Ophthalmology, Gartnavel General Hospital (Drs Irvine, Kumarasamy, and Kemp) and Department of Pathology, Western Infirmary (Dr Roberts), Glasgow, Scotland.


Arch Ophthalmol. 2012;130(8):1085-1087. doi:10.1001/archophthalmol.2012.422.
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Primary acquired melanosis (PAM) of the conjunctiva manifests as unilateral patchy areas of pigmentation usually in middle-aged or elderly patients. It can be differentiated histologically by the degree of atypia of melanocytes.1 Without atypia, PAM is a benign melanocytic proliferation. With atypia, PAM may progress to malignant melanoma. With severe atypia, PAM progresses to melanoma in about 13% of cases.1 We describe a case of PAM that progressed during pregnancy in a young patient.

A 28-year-old woman with brown irides had an 8 × 7-mm pigmented area on the right temporal bulbar conjunctiva (Figure 1A). She had noted this several years earlier but felt it was increasing in size.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Clinical photographs. A, Pigmented area of the right temporal bulbar conjunctiva prior to the first course of treatment. Arrow indicates biopsy site shown in Figure 2A. B, The pigmented area regressed following incisional biopsy and after completion of the first course of mitomycin C. C, Increase in the size of the pigmented area before the second course of mitomycin C. Arrow indicates biopsy site shown in Figure 2B. D, The pigmented area again regressed after incisional biopsy and completion of the second course of mitomycin C. E, The lesion showed a definite increase in size when the patient was followed up at 14 weeks' gestation. Arrow indicates biopsy site shown in Figure 2C. F, Significant improvement in the wound site and in the appearance of the pigmented area 1 month after childbirth, following excisional biopsy and cryotherapy. Arrow indicates biopsy site shown in Figure 2E.

The area was biopsied and showed PAM with moderate atypia (Figure 2A). She was treated with a standard 9-week course of topical mitomycin C, 0.04%, 4 times/d, prednisolone acetate eyedrops, 0.5%, 4 times/d, and ocular lubricants. The pigmented area regressed and remained stable during the next 18 months (Figure 1B). Seven months later, an increase in size and pigment density was noted (Figure 1C). A repeated biopsy showed PAM with moderate atypia (Figure 2B). It was treated with a second course of mitomycin C with good response (Figure 1D).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Histologic findings. A, Initial biopsy specimen from the pigmented area in Figure 1A showing atypical melanocytes within the lower half of the conjunctival epithelium (arrows), considered to be primary acquired melanosis with moderate atypia (hematoxylin-eosin, original magnification ×100). B, A similar appearance is seen in the repeated biopsy (from the area in Figure 1C) performed prior to the second course of mitomycin C (hematoxylin-eosin, original magnification ×100). Arrows indicate atypical melanocytes considered to amount to primary acquired melanosis with moderate atypia. C, Biopsy specimen from the area shown in Figure 1E, with almost confluent nests of atypical melanocytes along the epithelium, considered to be melanoma in situ (hematoxylin-eosin, original magnification ×100). D, Staining for melan A on the tissue shown in C also shows occasional positive cells in the stroma, suspicious of early invasion (arrows) (original magnification ×100). E, Biopsy specimen of the area in C following treatment. There was no obvious melanocytic process in the hematoxylin-eosin–stained section (original magnification ×40). F, Immunohistochemical staining showed an area with increased melanocytes within the epithelium (arrows), considered to be primary acquired melanosis with moderate atypia (melan A, original magnification ×40).

At follow-up 14 months later, definite growth of the area was documented (Figure 1E). The patient was 14 weeks' pregnant. Excision biopsy and cryotherapy were performed. Histologic analysis showed conjunctival melanoma in situ with suspicion of stromal invasion (Figure 2C and D). The lesion was closely monitored for the remainder of the pregnancy.

Seven months later, 1 month after childbirth, there was significant improvement at the wound site (Figure 1F). However, a repeated biopsy performed from a nonpigmented area showed PAM with atypia (Figure 2E and F).

Changes in cutaneous melanocytic lesions and progression to malignant melanoma during pregnancy are well documented.2 Similarly, conjunctival nevi have been documented to change during pregnancy. Progression of PAM with atypia during pregnancy has rarely been documented.3

Accelerated development of conjunctival melanoma during pregnancy may be simply coincidence. This has been postulated for cutaneous melanoma, although most studies suggest a genuine increased risk.4 The 2 main postulated theories for this increased risk are hormonal factors and decreased immunity. Several investigators have examined the role of sex hormone receptor status in conjunctival melanoma, PAM, and nevi.3,5,6 Chowers et al5 investigated 2 cases of conjunctival melanoma and 13 cases of PAM and were unable to detect estrogen receptors in any. Paridaens et al3 found that 6 of 15 conjunctival melanomas were estrogen receptor positive. More recently, Pache et al6 found expression of progesterone receptors in 96% of cases, consisting of 69 nevi, 5 cases of PAM, and 2 melanomas. Staining for estrogen and progesterone receptors was negative in this patient.

Changes in immunity that accompany pregnancy may also play an important role. To protect the fetus from rejection, pregnancy induces immunosuppression with a predominant T-helper 2 response to inciting stimuli. Indeed, the severity of many diseases has been shown to be affected by pregnancy. This anti-inflammatory response may also affect tumor surveillance and promote tumor growth. This reduction in immune surveillance has been suggested by Paridaens et al,3 who described a young woman with growth of conjunctival melanosis and melanoma during the course of 3 pregnancies.

An additional feature of concern in this patient was that the PAM was nonpigmented in some areas. While PAM sine pigmento is well recognized, often in conjunction with pigmented areas, it can be difficult to follow up.7

In conclusion, while this link with pregnancy and conjunctival melanoma progression cannot be fully explained, it would be prudent for young women with PAM with atypia to be closely monitored during reproductive life.

Correspondence: Dr Irvine, Department of Ophthalmology, Gartnavel General Hospital, 1053 Great Western Rd, Glasgow G12 0YN, Scotland (francesca.irvine@nhs.net).

Financial Disclosure: None reported.

Shields JA, Shields CL, Mashayekhi A,  et al.  Primary acquired melanosis of the conjunctiva: experience with 311 eyes.  Trans Am Ophthalmol Soc. 2007;105:61-72
PubMed
Driscoll MS, Grant-Kels JM. Nevi and melanoma in pregnancy.  Dermatol Clin. 2006;24(2):199-204, vi
PubMed   |  Link to Article
Paridaens DA, Alexander RA, Hungerford JL, McCartney ACE. Oestrogen receptors in conjunctival malignant melanoma: immunocytochemical study using formalin fixed paraffin wax sections.  J Clin Pathol. 1991;44(10):840-843
PubMed   |  Link to Article
Gandini S, Iodice S, Koomen E, Di Pietro A, Sera F, Caini S. Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis.  Eur J Cancer. 2011;47(17):2607-2617
PubMed   |  Link to Article
Chowers I, Livni N, Frucht-Pery J, Pe’er J. Immunostaining of the estrogen receptor in conjunctival primary acquired melanosis.  Ophthalmic Res. 1999;31(3):210-212
PubMed   |  Link to Article
Pache M, Glatz-Krieger K, Sauter G, Meyer P. Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.  Graefes Arch Clin Exp Ophthalmol. 2006;244(1):113-117
PubMed   |  Link to Article
Paridaens ADA, McCartney ACE, Hungerford JL. Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.  Br J Ophthalmol. 1992;76(3):163-165
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Clinical photographs. A, Pigmented area of the right temporal bulbar conjunctiva prior to the first course of treatment. Arrow indicates biopsy site shown in Figure 2A. B, The pigmented area regressed following incisional biopsy and after completion of the first course of mitomycin C. C, Increase in the size of the pigmented area before the second course of mitomycin C. Arrow indicates biopsy site shown in Figure 2B. D, The pigmented area again regressed after incisional biopsy and completion of the second course of mitomycin C. E, The lesion showed a definite increase in size when the patient was followed up at 14 weeks' gestation. Arrow indicates biopsy site shown in Figure 2C. F, Significant improvement in the wound site and in the appearance of the pigmented area 1 month after childbirth, following excisional biopsy and cryotherapy. Arrow indicates biopsy site shown in Figure 2E.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Histologic findings. A, Initial biopsy specimen from the pigmented area in Figure 1A showing atypical melanocytes within the lower half of the conjunctival epithelium (arrows), considered to be primary acquired melanosis with moderate atypia (hematoxylin-eosin, original magnification ×100). B, A similar appearance is seen in the repeated biopsy (from the area in Figure 1C) performed prior to the second course of mitomycin C (hematoxylin-eosin, original magnification ×100). Arrows indicate atypical melanocytes considered to amount to primary acquired melanosis with moderate atypia. C, Biopsy specimen from the area shown in Figure 1E, with almost confluent nests of atypical melanocytes along the epithelium, considered to be melanoma in situ (hematoxylin-eosin, original magnification ×100). D, Staining for melan A on the tissue shown in C also shows occasional positive cells in the stroma, suspicious of early invasion (arrows) (original magnification ×100). E, Biopsy specimen of the area in C following treatment. There was no obvious melanocytic process in the hematoxylin-eosin–stained section (original magnification ×40). F, Immunohistochemical staining showed an area with increased melanocytes within the epithelium (arrows), considered to be primary acquired melanosis with moderate atypia (melan A, original magnification ×40).

Tables

References

Shields JA, Shields CL, Mashayekhi A,  et al.  Primary acquired melanosis of the conjunctiva: experience with 311 eyes.  Trans Am Ophthalmol Soc. 2007;105:61-72
PubMed
Driscoll MS, Grant-Kels JM. Nevi and melanoma in pregnancy.  Dermatol Clin. 2006;24(2):199-204, vi
PubMed   |  Link to Article
Paridaens DA, Alexander RA, Hungerford JL, McCartney ACE. Oestrogen receptors in conjunctival malignant melanoma: immunocytochemical study using formalin fixed paraffin wax sections.  J Clin Pathol. 1991;44(10):840-843
PubMed   |  Link to Article
Gandini S, Iodice S, Koomen E, Di Pietro A, Sera F, Caini S. Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis.  Eur J Cancer. 2011;47(17):2607-2617
PubMed   |  Link to Article
Chowers I, Livni N, Frucht-Pery J, Pe’er J. Immunostaining of the estrogen receptor in conjunctival primary acquired melanosis.  Ophthalmic Res. 1999;31(3):210-212
PubMed   |  Link to Article
Pache M, Glatz-Krieger K, Sauter G, Meyer P. Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva.  Graefes Arch Clin Exp Ophthalmol. 2006;244(1):113-117
PubMed   |  Link to Article
Paridaens ADA, McCartney ACE, Hungerford JL. Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.  Br J Ophthalmol. 1992;76(3):163-165
PubMed   |  Link to Article

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