UV-induced pigmentation (suntanning) requires induction of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes. alpha-MSH and other bioactive peptides are cleavage products of pro-opiomelanocortin (POMC). Here we provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces beta-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic pigmentation are shown to involve p53 "mimicking" the tanning response. p53 thus functions as a sensor/effector for UV pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response.

We studied the cases of 353 patients with lymphoma involving the ocular adnexa diagnosed at the Massachusetts General Hospital between 1974 and 2005. The patients included 153 males and 200 females, aged 7 to 95 years, with a mean age of 64 years. In 277 cases, there was no known history of lymphoma. Seventy-six patients had a history of lymphoma, with the ocular adnexa being involved at relapse or with progression of the previously diagnosed lymphoma. The patients had marginal zone lymphoma (182 cases), follicular lymphoma (80 cases), mantle cell lymphoma (18 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (13 cases), lymphoplasmacytic lymphoma (4 cases), splenic marginal zone lymphoma (2 cases), low-grade B cell, not subclassified (19 cases), precursor B lymphoblastic lymphoma (3 cases), diffuse large B-cell lymphoma (26 cases), and 1 case each of high-grade B-cell lymphoma, not subclassified, peripheral T-cell lymphoma, unspecified type, extranodal NK/T-cell lymphoma, nasal type, and Hodgkin lymphoma, nodular sclerosis type. Almost all marginal zone lymphoma patients (168 of 182, 92%) had primary ocular adnexal lymphoma. Fourteen marginal zone lymphoma patients (8%) had a prior history of lymphoma, usually arising in another extranodal site. Twenty-five of 80 (31%) follicular lymphoma patients had a prior history of lymphoma, usually arising in lymph nodes. Patients with mantle cell lymphoma, chronic lymphocytic leukemia, lymphoplasmacytic lymphoma, and splenic marginal zone lymphoma almost always had a prior history of lymphoma or were known to have widespread disease at the time of diagnosis of ocular adnexal lymphoma. A subset of the diffuse large B-cell lymphomas were associated with large destructive masses involving adjacent structures such as paranasal sinuses, raising the possibility that they may have arisen from one of the adjacent structures and involved the ocular adnexa by direct extension. The relatively high proportion of low-grade lymphoma, not subclassified, highlights the difficulty that may arise in distinguishing different types of low-grade lymphoma, particularly when biopsies are small and artifactually distorted. Ocular adnexal lymphoma is primarily a disease of older adults, with a slight female preponderance. Most lymphomas are low-grade B-cell lymphomas, with marginal zone lymphoma being by far the most common type. Marginal zone lymphoma typically involves the ocular adnexa primarily, whereas other types of low-grade B-cell lymphoma often involve the ocular adnexa secondarily. High-grade B-cell lymphomas only occasionally involve the ocular adnexa, and T-cell lymphoma, NK-cell lymphoma, and Hodgkin lymphoma are only rarely encountered in this site.

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