Ian W. McLean

Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumour cells.

A reappraisal of survival data on patients with uveal melanomas has led us to these impressions: (a) that the mortality rate before enucleation is low, estimated at 1% per year; (b) that the mortality rate rises abruptly following enucleation, reaching a peak of about 8% during the second year after enucleation; and (c) that approximately two-thirds of the fatalities could be attributed to the dissemination of tumour emboli at the time of enucleation. From these impressions we believe the following conclusions are warranted: (a) enucleation as it has been performed in the past may have for many patients an adverse rather than a beneficial effect with respect to the development of metastatic disease from malignant melanoma of the choroid and ciliary body. (b) A long-term follow-up study of untreated patients with melanomas of the choroid and ciliary body is indicated. (c) New techniques for enucleation designed to prevent the dissemination of tumour cells must be developed and tested to enable the ophthalmic surgeon to remove safely the tumour-containing eye that has developed such complications as uncontrollable glaucoma, panophthalmitis, or proptosis from extraocular extension.

Modifications of Callender's Classification of Uveal Melanoma at the Armed Forces Institute of Pathology

One hundred well-documented cases of uveal melanoma accessioned at the Armed Forces Institute of Pathology before 1970 were reviewed and reclassified to identify changes made in the Callender classification. We compared the new classification with the original classification to determine the effect of the changes on the prediction of outcome for the patient after enucleation. Staff pathologists had originally classified 52 of the 100 cases as spindle-cell type melanoma. Only 31 of the 100 cases were reclassified as spindle-cell types (two spindle-cell nevi and 29 spindle-cell melanomas). Tumors classified as mixed-cell type were further subdivided into groups based on the percentage and size of the epithelioid cells. Tumors formerly classified as spindle-cell type that contained small or rare epithelioid cells were reclassified as mixed-cell type. This improved the prediction of outcome for the patient. We found that nucleolar size and pleomorphism are important variables that should be considered in the classification of uveal melanomas.

Incidence of Second Neoplasms in Patients with Bilateral Retinoblastoma

The cumulative incidence of second neoplasms in 215 patients with bilateral retinoblastoma was calculated using the life-table method. Second tumors developed in 4.4% of the patients during the first 10 years of follow-up, in 18.3% after 20 years, and in 26.1% after 30 years. The 30-year cumulative incidence was 35.1% for the 137 patients who received radiation therapy compared with an incidence rate of 5.8% for the 78 patients who did not receive radiation. In the 137 patients who received radiation, second tumors developed both inside and outside the field of therapy. There was a 30-year incidence rate of second tumors of 29.3% within the field of irradiation and 8.1% outside the field. The rate outside the field of irradiation (8.1%) was similar to that observed in nonirradiated patients (5.8%). Our findings indicate that carriers of the retinoblastoma gene have an increased incidence of second tumors, and that the incidence rate is further increased in patients who receive radiation therapy.

An Evaluation of Enucleation in the Management of Uveal Melanomas

Uveal melanomas are slow growing tumors that may infiltrate out of the eye, mainly following ciliary vessels or nerves, or invade blood vessels, but only rarely do they produce metastatic disease before discovery and treatment. There are, however, large gaps in our knowledge of the frequency and rate of growth of small tumors to those of moderate or large size. We have estimated the mortality from untreated uveal melanomas to be 1% per year or less. Almost all information concerning prognostic factors has been gained from studies based on cases treated by enucleation. The same information is not necessarily applicable to untreated tumors. A study of deaths from metastatic uveal melanomas reveals a striking relationship to enucleation, regardless of whether one deals with cases in which the eye had been symptomatic for a long or short time. Following a low preoperative mortality of 1% or less, the annual mortality rises to about 4% during the first year and then peaks at 8 to 12% during the second year, tapering off during the next three to five years to return to a remarkably constant level of 1 to 2% thereafter. We postulated that this relationship of peak mortality to enucleation is attributable mainly to an often overwhelming dissemination of tumor cells taking place during surgery or to a lowering of the hosts immunologic defense mechanisms as a consequence of the operation, or both. We urge the pooling of all available information gained from clinical studies made on untreated tumors and recommend prospective studies of a variety of other methods of treating uveal melanomas in addition to the standard enucleation.

Malignant melanoma of the conjunctiva

One hundred thirty-one cases of conjunctival melanoma in which biopsies had been performed were studied to determine potential factors that might affect outcome in patients with these lesions. Two groups of lesions were identified: those associated with primary acquired melanosis (melanoma with PAM, 98 cases, 74.8 per cent) and those without primary acquired melanosis (melanoma without PAM, 33 cases, 25.2 per cent). The overall mortality rate in the 131 cases was 26 per cent (34 of 131); the mortality rate due to melanoma with PAM was 25.5 per cent (25 of 98), and that due to melanoma without PAM was 27.3 per cent (9 of 33). If PAM was associated with the lesion, the presence of atypical melanocytes within the epithelium (pagetoid invasion) was a sensitive indicator of subsequent metastasis. Tumor thickness may also be useful for predicting subsequent metastases. None of the histologic parameters studied proved useful for predicting outcome in patients who had melanomas without PAM. The presence or absence of nevi had no effect on prognosis.

Primary acquired melanosis of the conjunctiva

Forty-one cases of conjunctival primary acquired melanosis (PAM) were studied to determine the frequency of progression to malignant melanoma and to establish prognostic parameters for progression to melanoma. Two subdivisions were identified: lesions with cytologically atypical melanocytes (PAM with atypia, 28 lesions, 68.3 per cent) and those lacking cytologically atypical melanocytes (PAM without atypia, 13 lesions, 31.7 per cent). None of the lesions of PAM without atypia progressed to melanoma. Thirteen of the 28 lesions of PAM with atypia (46.4 per cent) progressed to melanoma. Progression to melanoma was more frequent in the lesions of PAM with atypia if basilar hyperplasia was not the dominant histologic pattern (90 per cent progression, P = 0.02) or if any epithelioid cells were present (75 per cent progression, P = 0.02). It was not possible to determine which lesions were atypical on the basis of clinical appearance. Lesions at risk for the development of melanoma should be totally extirpated.

Lymphocytic infiltration in uveal malignant melanoma

A study relating the intralesional infiltration of lymphocytes and plasma cells to patient survival was performed on cases of uveal malignant melanoma accessed at the Armed Forces Institute of Pathology, Washington, DC (AFIP) between 1954 and 1971. The authors examined 1193 cases using light microscopy. Of the 1078 cases with technically acceptable histologic sections, 134 tumors contained 100 or more lymphocytes per 20 high‐power (X400) microscopic fields (20 HPF). The prevalence was 12.4%. This was designated the “high lymphocytic” group. An equivalent number of cases with fewer lymphocytes comprised the “low lymphocytic” group. The survival rate at 15 years was 36.7% for patients in the high lymphocytic group and 69.6% for patients in the low lymphocytic group. Using the Cox model, the authors found that an increased number of lymphocytes per 20 HPF was significantly associated with decreased survival (chi‐square = 21.2, P = <0.0001). A significant association was observed even when we controlled for other risk factors (chi‐square = 6.98, P = 0.008).

Cowden's Disease

Cowdens disease, or multiple hamartoma syndrome, is a rare genodermatosis. Multiple facial trichilemmomas, acral keratoses, and oral papillomas are the most common mucocutaneous lesions in this disease. It is associated with increased rates of cancer of the breast and thyroid as well as benign tumors and hamartomas of multiple organ systems. Multiple facial trichilemmomas are essentially pathognomonic of this syndrome and may appear as lesions of the eyelid and periorbital skin. A case of Cowdens disease is described and previously reported cases reviewed, with emphasis on the ocular aspects of the disease.

Reappraisal of Callender'S Spindle a Type of Malignant Melanoma of Choroid and Ciliary Body

A follow-up study and histologic reevaluation were made of 105 melanomas of the choroid and ciliary body that had originally been classified as Callenders spindle A type. There were 18 deaths attributable to tumor, with metastatic disease confirmed by autopsy or biopsy in eight cases. We were able to separate the 105 melanomas histopathologically into three groups. The first group consisted of 15 cases in which the spindle-shaped tumor cells were cytologically benign; no deaths were observed for this group. The 75 tumors in the second group were composed of spindle cells, but differed from those in the first group by their malignant features, namely, more atypicality of cells, mitotic activity, necrosis, invasion into sclera or through Bruchs membrane, larger size of the tumor, or any combination of the above. The prognosis for this group was good, comparable to that of spindle B melanomas. The 15 tumors in the third group contained epithelioid cells and had a poor prognosis, comparable to that of mixed-cell melanomas.

Conjunctival Melanosis and Melanoma

A clinicopathologic study of 41 cases of primary acquired melanosis has provided information concerning the rate of progression to melanoma and has provided histologic parameters useful in predicting which lesions are likely to progress to malignant melanoma. A clinicopathologic study of 131 conjunctival melanomas has provided information concerning the clinical and histologic parameters associated with a fatal outcome. Highlights of these two studies are presented together with implications for diagnosis and therapy.