Letter to the Editor
Rapid growth of choroidal melanoma during pregnancy*
Article first published online: 24 NOV 2009
Journal compilation © 2009 Acta Ophthalmol
Volume 89, Issue 3, pages e290–e291, May 2011
How to Cite
Lee, C. S., Yang, W. I., Shin, K.-J. and Lee, S. C. (2011), Rapid growth of choroidal melanoma during pregnancy*. Acta Ophthalmologica, 89: e290–e291. doi: 10.1111/j.1755-3768.2009.01803.x
- Issue published online: 24 NOV 2009
- Article first published online: 24 NOV 2009
A 29-week pregnant, 31-year-old woman presented with a superior juxtapapillary choroidal tumour (8 mm largest basal diameter (LBD) × 5 mm height) in her left eye with a visual acuity of 20/30 (Fig. 1A, B). The patient wanted to delay any treatment until delivery. Three months later (2 weeks after delivering a boy), the tumour size had increased to 13 mm × 12 mm. There was extensive serous retinal detachment and subretinal haemorrhage that reduced her visual acuity to detecting only hand motion (Fig. 1C, D). Pathology of enucleated eye confirmed choroidal melanoma of mixed cell type and fluorescence in situ hybridization for chromosome 3 indicated monosomy (ZytoVision, Bremerhaven, Germany). Immunohistochemistry indicated absence of both oestrogen (Thermo Scientific, SP1, 1:100) and progesterone receptors (Dako, PgR 636, 1:100). The mean microvascular density (MVD) from three most highly vascularized areas (CD34+) was 79 vessels/0.313 mm2. Using standard photographs for semiquantitative scoring system (Makitie et al. 2001), macrophage density (CD68+) was determined to be moderate.
We suspected that male foetal cells from the maternal circulation participated in tumour angiogenesis; however, there was no Y chromosome detected in the tumour using a DNA quantification kit (Applied Biosystems, Foster city, CA, USA). The patient was monitored for 2 years and remains metastasis free.
The median doubling time for epithelioid cell containing primary uveal melanoma (UM) ranges from 111 days (of nine mixed cell melanoma) (Augsburger et al. 1984) to 330 days (of 13 mixed cell or epithelioid melanoma) (Gass 1985). The tumour doubling time in our case was 34 days. Assuming an ellipsoidal form and constant exponential growth rate of the tumour, the volume and doubling time were calculated as follows:
We assumed that the LBD represented both tumour length and width.
Although it could have been coincidental, the growth of UM during pregnancy have been previously reported (Seddon et al. 1982), as has transformation of clinically stable choroidal nevus into melanoma during pregnancy (Shields et al. 1991). Despite suspicions that increased growth was the result of endocrine effects, we did not detect oestrogen or progesterone receptors, which is consistent with previous studies (Seddon et al. 1982). In addition to rising oestrogen and progesterone, secretion of melanocyte-stimulating hormone (MSH) also increases during pregnancy. MSH is responsible for hyperpigmentation in pregnant women, usually affecting the nipples, areola, and face. UM is of melanocytic origin, so it has the potential to respond to elevated MSH.
During pregnancy, immunity is altered to favour type 2 helper cell pathway (Th2) over type 1 helper cell pathway (Th1)to tolerate the foetus. This Th1/Th2 imbalance could promote rapid tumour growth.
Vascular changes are frequently observed during pregnancy because of increased blood volume and raised angiogenic factors from high demand of vascular placenta. Although these vascular changes can merely increase tumour oedema or subretinal exudation, they can promote tumour vascularity as well, which facilitates growth. MVD was relatively high in our case, considering median MVD of 40 vessels/0.313 mm2 for 134 UM in one series (Makitie et al. 1999).
Tumour vascularity is also affected by foetal cell microchimerism; foetal progenitor cells can enter the maternal circulation, and a recent study reported that these cells engraft in maternal cutaneous melanoma and differentiate into endothelial cells (Nguyen Huu et al. 2009). However, we did not detect foetal cells in the tumour.
Therefore, the mechanism for rapid growth of UM in our patient may be multifactorial, relating to complex endocrine signalling, altered immunity, and a favourable angiogenic environment. The cumulative mortality rate depends on the tumour size. We recommend that a newly diagnosed UM in pregnant state be re-examined in one month if the tumour is to be observed. Initiation of the treatment is warranted in rapidly enlarging tumours.
Part of this work was presented at the International Congress of Ocular Oncology conference from the 8–12th of September 2009 in Cambridge, United Kingdom.
- 1984): Growth rates and doubling times of posterior uveal melanomas. Ophthalmology 91: 1709–1715. , , , & (
- 1985): Comparison of uveal melanoma growth rates with mitotic index and mortality. Arch Ophthalmol 103: 924–931. (
- 1999): Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma. Invest Ophthalmol Vis Sci 40: 2471–2480. , , & (
- 2001): Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci 42: 1414–1421. , , & (
- 2009): Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol 174: 630–637. , , et al. (
- 1982): Uveal melanomas presenting during pregnancy and the investigation of oestrogen receptors in melanomas. Br J Ophthalmol 66: 695–704. , , , & (
- 1991): Uveal melanoma and pregnancy. A report of 16 cases. Ophthalmology 98: 1667–1673. , , , & (