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Primary acquired melanosis (PAM) presents as a unilateral

neoplastic melanocytic proliferation within the conjunctival

epithelium characterized by patchy area of

conjunctival pigmentation (yellow brown stippling

within the epithelium).

It has been suggested by some authors that "

"primary acquired melanosis" (PAM) of the conjunctiva 

and its analogs, namely, lentigo melanosis (Hutchinson),

 melanotic freckle (Hutchinson), melanose circonscrite

precancereuse (Dubrueilh), melanotische precancerose

(Miescher), lentigo maligna (Clark), precancerous

melanosis (Reese), benign, precancerous, and

cancerous melanosis (Zimmerman), atypical melanocytic

hyperplasia (Silver et al.), and benign acquired melanosis

(Zimmerman), are synonyms for melanoma in situ.

"Primary acquired melanosis,"  is not simply a condition of

blackening by melanin, but a flat melanoma that, if not

removed  completely, may give rise one day to metastases

that cause death.

"Primary acquired melanosis,"  is mostly found in middle-aged

or elderly white patients.

It is predominantly a proliferative condition of the melanocytes

that normally populate the conjunctival epithelium.

Although bulbar conjunctival involvement is most common,

any part  of the conjunctiva, including the non-exposed

fornical, palpebral  and canthal regions, may be affected.

Because PAM has the potential of becoming malignant,

it is important to recognize PAM and to rule out other

causes of pigmented lesions.

The presence or absence of atypia is helpful in determining

the potential for malignancy, because PAM without

atypia is usually benign, whereas PAM with atypia may convert

into a conjunctival melanoma.

If atypia is present, the presence or absence of epithelioid cells

and the pattern of intraepithelial growth are the main

factors in determining the likelihood of neoplastic

transformation. The lesion is usually flat, which distinguishes

it from nevi and melanomas which are elevated.

When elevated lesions develop in PAM they are usually a

sign of malignancy.

The elevation of PAM is unpredictable.

It often progresses slowly, but may wax or wane.

Clinical evaluation by simple inspection and slit-lamp

examination may not reveal the full extent

of the melanosis.

Using ultraviolet light, areas of subclinical melanosis

may be identified, extending far beyond the edges of

the obvious lesion. The histologic features of PAM are

extremely variable, not only in different cases but in

different areas within a lesion.

The melanocytes vary in size, shape, and degree of atypia.

They may be small polyhedral cells with no atypia, or large,

highly atypical epithelioid cells.

The pattern of involvement also varies.

Individual melanocyte may line up along the basal

lamina of the epithelium, form nests of melanocytes

extending into the epithelium in a pagetoid fashion,

or completely replace the epithelium with atypical

melanocytes mimicking an in situ-carcinoma.

When melacocytes invade the epithelium in a pagetoid

fashion or replace the epithelium, the risk of melanoma

is approximately 90%.

When they are confined to the basal layer of the epithelium,

the risk of that lesion developing into a melanoma

is around 20%.

75 % of tumours that contain epithelioid cells progress

to melanoma.

Lesions in which no or only minimal atypia can be detected

seem not to progress to melanoma.

Primary acquired melanosis in an adult should not be

confused with "a junctional nevus," which is almost

always restricted to childhood. A combination of surgical

excision and cryotherapy is the most widely recommended

treatment for conjunctival primary acquired melanosis

with atypia.

Recently, topical chemotherapy with mitomycin-C eye drops

has been established as a therapeutic option.

Visit: Conjunctival Melanocytic Tumours ; Conjunctival Nevus ; Conjunctival Melanoma ;  Uveal Melanoma .

             

Primary acquired melanosis of the conjunctiva.Optometry. 2006 May;77(5):223-8.

BACKGROUND: Primary acquired melanosis (PAM) presents as a unilateral patchy area of conjunctival pigmentation mostly found in middle-aged or elderly white patients. Because PAM has the potential of becoming malignant, it is important to recognize PAM and to rule out other causes of pigmented lesions. The presence or absence of atypia is helpful in determining the potential for malignancy, because PAM without atypia is usually benign, whereas PAM with atypia may convert into a conjunctival melanoma. If atypia is present, the presence or absence of epithelioid cells and the pattern of intraepithelial growth are the main factors in determining the likelihood of neoplastic transformation. However, atypia can only be determined with histopathologic examination. Therefore, a biopsy is usually recommended. CASE REPORT: A 72-year-old white man presented for his annual examination with no visual complaints. His ocular history was remarkable for early cataracts and for a choroidal nevus. Slit lamp examination found a large dark area of elevated conjunctival pigmentation at the medial canthus that extended onto the superior bulbar conjunctiva and superior palpebral conjunctiva in the left eye. No conjunctival pigmentation had been noted previously. Results of a biopsy indicated primary acquired melanosis with atypia. The lesion was surgically excised, and the conjunctiva was reconstructed with an amniotic membrane graft. The patient was subsequently treated with topical 5-fluorouracil chemotherapy. There have been no signs of recurrence to date after his treatment. CONCLUSION: Because of the potential for malignancy, biopsies of all cases of primary acquired melanosis are indicated. If atypia is present, treatment options include local excision, cryotherapy, and topical chemotherapy.

Conjunctival primary acquired melanosis.Tidsskr Nor Laegeforen. 2005 Sep 22;125(18):2480-2.

BACKGROUND: Pigmented lesions of the conjunctiva may represent primary acquired melanosis. If histological examination reveals atypical melanocytes in the epithelial layer of the conjunctiva, there is a close to 50% risk of transformation to a conjunctival malignant melanoma. A combination of surgical excision and cryotherapy is the most widely recommended treatment for conjunctival primary acquired melanosis with atypia. Recently, topical chemotherapy with mitomycin-C eye drops has been established as a therapeutic option. MATERIAL AND METHODS: Based on two case reports and a review of the literature, clinical aspects and the use of topical chemotherapy are presented. RESULTS AND INTERPRETATION: Pigmented conjunctival lesions arising in adults may represent primary acquired melanosis with atypia. In patients with large or multiple pigmentations, extensive surgery with cryotherapy is necessary. In such circumstances, topical chemotherapy with mitomycin-C eye drops is a good alternative and may lead to complete regression, as in our two patients.

Immunostaining of the estrogen receptor in conjunctival primary acquired melanosis. Ophthalmic Res. 1999;31(3):210-2.

Conjunctival primary acquired melanosis (PAM) is a frequent precursor of conjunctival melanoma. Since there is indirect evidence that the conjunctiva is an estrogen-responsive tissue, and since it was suspected that estrogen has a role in the etiology of melanoma, we decided to evaluate whether PAM may be responsive to estrogen. Formalin-fixed, paraffin-embedded sections from 13 cases of PAM and 2 cases of conjunctival melanoma were immunostained with an estrogen-receptor (ER)-specific antibody. All lesions and the normal conjunctival tissue adjacent to the lesions were found to be ER negative. It is concluded that PAM and normal conjunctiva are not sensitive directly to estrogen. When considering previously reported data, it is conceivable that the normal conjunctiva, but not PAM, is indirectly affected by estrogen.

Primary acquired melanosis of the conjunctiva is melanoma in situ.Mod Pathol. 1991 Mar;4(2):253-63.

This essay places the concept of "primary acquired melanosis" of the conjunctiva in historical perspective and shows that it and its analogs, namely, lentigo-melanosis (Hutchinson), melanotic freckle (Hutchinson), melanose circonscrite precancereuse (Dubrueilh), melanotische precancerose (Miescher), lentigo maligna (Clark), precancerous melanosis (Reese), benign, precancerous, and cancerous melanosis (Zimmerman), atypical melanocytic hyperplasia (Silver et al.), and benign acquired melanosis (Zimmerman), are synonyms for melanoma in situ. The issue is not merely semantic or philosophical; it is urgently practical. If a clinician takes literally the meaning of a lesion designated "benign melanosis" and considers it to be benign, rather than the malignant melanoma that it actually is, a patient who bears that flat pigmented lesion may one day die of metastasis from an elevated sequella of it. The same is true of "primary acquired melanosis," which is not simply a condition of blackening by melanin, but a flat melanoma that, if not removed completely, may give rise one day to metastases that cause death. To avoid such misconstructions, we advocate naming melanomas in all organs "melanoma" and those that are confined to epithelial structures "melanoma in situ." Euphemisms like lentigo maligna and primary acquired melanosis are evasions of the diagnosis of melanoma, and use of them may be harmful. For that reason, they should be eschewed.

Clinicopathologic characteristics of premalignant and malignant melanocytic lesions of the conjunctiva.Ophthalmology. 1989;96(2):147-66.

Primary acquired melanosis (PAM), a disease that affects mostly middle-aged white patients, is predominantly a proliferative condition of the melanocytes that normally populate the conjunctival epithelium. Primary acquired melanosis without atypia (low risk for the development of melanoma) is typically created by increased numbers of melanocytes restricted to the basilar region of the epithelium without nuclear hyperchromasia or prominence of the nucleoli. Primary acquired melanosis with atypia, a formal precursor of melanoma, is characterized by the proliferation of small polyhedral cells, spindle cells, large dendritiform melanocytes, or epithelioid cells that may: remain restricted to the basilar region (basilar nests); form nests at all levels of the epithelium; spread individually to all levels of the epithelium (pagetoid extension); or proliferate in a sheet-like fashion approximating a melanoma in situ. Lesions composed of epithelioid cells or exhibiting intraepithelial pagetoid extension have, respectively, a 75 or 90% chance of eventuating in invasive melanoma. Primary acquired melanosis in an adult should not be confused with "a junctional nevus," which is almost always restricted to childhood. Invasive melanomas measuring less than 0.8 mm in thickness tend not to be associated with metastases; the tumor cells may be small polyhedral (in which case confusion with a compound nevus often arises), epithelioid, spindled, or ballooned. Nodules composed of spindle cells in part or in toto tend to have less metastatic potential at a given thickness measurement than comparable nodules composed of epithelioid or polyhedral cells. The clinical features, electron microscopic findings, and biologic principles underwriting clinical management are also presented.

Primary acquired melanosis of the conjunctiva.Hum Pathol. 1985 Feb;16 (2):129-35.

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.

Idiopathic acquired melanosis. Ophthalmology. 1980 Aug;87(8):835-40.

Acquired melanosis is the clinical term used to describe a slowly enlarging, diffusely pigmented lesion of the conjunctiva which may also involve the lids, caruncle or cornea. The controversial histologic classifications are reviewed and suggestions made regarding useful and accurate terminology. In acquired melanosis, development of malignant melanoma may occur. Previous work indicates that the prognosis of the resulting melanoma may be assessed by histopathologic staging as is done in cutaneous melanoma. The suggested management of acquired melanosis is close observation with excisional biopsies of areas clinically suggestive of invasive melanomas. Examination of the entire biopsy by serial or staged sections is essential for accurate histopathologic diagnosis. Invasive melanomas have been conventionally treated by local excision or exenteration. Radiation therapy may be a beneficial adjunct.

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