Brain Pathology Case of the Month - June 2010


  1. Epithelioid and spindle cell conjunctival melanoma
  2. Metastatic epithelioid and spindle cell conjunctival melanoma


Malignant melanoma is a potentially fatal tumor that arises from melanocytes, most often in the sun exposed skin (1). Less commonly, melanoma originates from other tissues and mucous membranes such as conjunctiva. Conjunctival melanoma represents only 1.6% of all non-cutaneous melanoma, being the most infrequent of the ocular melanomas (8). It is proposed to originate from preexisting conjunctival nevus (as Ota's nevus) or primary acquired melanosis (PAM) or melanoma de novo (10). On the other hand, ooccupational skin cancers resemble skin tumors found in non-occupational subjects (including melanoma) and have particularly been due to industrial exposure of human beings to chemical carcinogens such as arsenic, ionizing radiation such as X-rays and polycyclic hydrocarbons (e.g. from coal tar products). Besides, an uncommon but well-recognized cause of occupational skin cancer is that which results from scar formation following an industrial burn(5). Some of that mechanism might have promoted the appearance of the initial conjunctival lesion in our case. The most important factors that affect patient outcome include greater tumor thickness and base, epithelioid cell type, and, if PAM is present along with the melanoma, then the following factors are significantly related to patient death: the presence of atypical melanocytes, pagetoid invasion, in situ growth pattern, caruncular and palpebral involvement, rarity of small polyhedral cell, lack of inflammation and high mitotic activity (4,9). Recurrence has been related to tumors not touching the limbus (extralimbal) (7,10), extension to the margins on histopathology (10) development of metastasis and treatment modality of the primary tumour (7). Therefore, proper surgical planning with wide tumor free margins is important (7,10). Usually, conjunctival melanomas, like those of the skin, first metastasize to draining regional lymph nodes, being the preauricular chain the most commonly involved (3), although distant metastasis in lung, liver, digestive tract, brain, bones, glands and skin have been reported (3,7,10). Development of metastasis has been related to tumors not touching the limbus (extralimbal) (10), extension to the margins on histopathology (10), tumour thickness over 2mm (7) and multilocular tumors (7). Isolated distant metastases (without evidence of prior or concurrent regional lymph node involvement) have been reported, especially in patients with history of local recurrence. The presence of more aggressive histological features in recurrent melanoma could enable tumor cells to skip the lymph nodes. On the other hand, hematogenous spreading to distant organs may occur following multiple surgical interventions for recurrence (2,3). Based on it, our patient did not show perioperative evidences to become a candidate for isolated distant metastases. The diagnosis of metastatic conjunctival melanoma requires close ophthalmological and systemic follow up at regular interval. High index of suspicion along with typical MRI findings help to confirm the diagnosis. Melanin produces stable free radicals, causing paramagnetic effect that shortens T1 and T2 relaxion values on MRI. This results in hyperintensity of the lesion on T1 and T2-weighted images (6).


  1. Clark WH Jr, Elder DE, Guerry D 4th, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984 15(12):1147-1165.
  2. De Potter P, Shields CL, Shields JA, Menduke H. Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases. Br J Ophthalmol. 1993 77(10):624-30.
  3. Esmaeli B, Wang X, Youssef A, Gershenwald JE. Patterns of regional and distant metastasis in patients with conjunctival melanoma: experience at a cancer center over four decades. Ophthalmology. 2001 108(11):2101-2105.
  4. Fuchs U, Kivelä T, Liesto K, Tarkkanen A. Prognosis of conjunctival melanomas in relation to histopathological features. Br J Cancer. 1989 59(2):261-267.
  5. Gawkrodger DJ. Occupational skin cancers. Occup Med 2004 54(7):458-463.
  6. Gomori JM, Grossman RI, Shields JA, Ausberger JJ, Joseph PM, DeSemione D. Choroidal melanomas: Correlation of NMR spectroscopy and MR imaging. Radiology 1986 158(2):443-445.
  7. Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci. 2005 46(1):75-82.
  8. Scotto J, Fraumeni JF Jr, Lee JA. Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. J Natl Cancer Inst. 1976 56(3):489-491.
  9. Seregard S, Kock E. Conjunctival malignant melanoma in Sweden 1969-91. Acta Ophthalmol 1992 70(3):289-296.
  10. Shields CL, Shields JA, Gündüz K, Cater J, Mercado GV, Gross N, Lally B. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Arch Ophthalmol. 2000 118(11):1497-1507.

Contributed by by Julio César Gutiérrez Morales, MD, PhD, Sandra Eugenia Gutiérrez Morales and Aurora Astudillo González, MD, PhD

International Society of Neuropathology