Progression of Primary Acquired Melanosis With Atypia During Pregnancy

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.

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).

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).