Subcutaneous Metastatic Adenocarcinoma: An Unusual Presentation of Colon Cancer - Case Report and Literature Review.

Subcutaneous metastasis from a visceral malignancy is rare with an incidence of 5.3%. Skin involvement as the presenting sign of a silent internal malignancy is an even rarer event occurring in approximately 0.8%. We report a case of a patient who presented to her dermatologist complaining of rapidly developing subcutaneous nodules which subsequently proved to be metastatic colon cancer, and we provide a review of the literature.

Long-term outcome of patients with a negative work-up for asymptomatic microhematuria.

OBJECTIVES: To assess the validity of the American Urological Association guidelines, we investigated 14-year outcomes of men aged > or = 50 years who had hematuria detected in a bladder cancer (BC) screening trial, were thoroughly evaluated, and were not found to have urological cancers. The American Urological Association guidelines for follow-up of adults with asymptomatic microhematuria (MH) who have negative evaluations include repeat urinary cytologies, urinalyses, and office visits for several years, primarily to detect BC (Cohen and Brown, N Engl J Med 348: 2330-2338, 2003; and Grossfeld et al, Urology 57:604-610, 2001). METHODS: Of 1575 screening participants, 258 had MH detected by daily home testing with the Ames hemastix during two 14-day periods. This test has been shown to accurately reflect MH on microscopic urinalysis when each is correctly performed. Any man with at least 1 positive test (> or = "trace") underwent a complete evaluation including microscopic urinalysis, culture, cytology, complete blood count, serum creatinine, coagulation profile, intravenous urography or computed tomography scan, and cystoscopy. BC or other urological tumors was not detected in 234 participants. Using Wisconsin state tumor registry and death certificate data, the outcomes of these men were tracked for 14 years since their last testing. RESULTS: Two of the 234 men (0.85%) developed BC during the 14-year follow-up, at 6.7 and 11.4 years after their negative evaluations; one died of BC 7.6 years after his last screening. During this follow-up, 0.93% of the screenees who tested negatively for hematuria had BC diagnosed, none within a year of their last testing date. CONCLUSIONS: Patients who have negative complete evaluations for asymptomatic MH have little chance of subsequently developing BC. The recommended "appropriate" follow-up for these patients may require reconsideration in light of these data.

Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression.

Melanocytes are progenitor cells for melanoma, which arises through step-wise progression from dysplastic to invasive, to metastatic tumor. Our previous data showed that semaphorin 7A (Sema7A), a protein involved in axon guidance, stimulates melanocyte adhesion and dendricity through opposing actions of beta1-integrin and Plexin C1 receptors. We now show that Plexin C1 is diminished or absent in human melanoma cell lines; analysis of tissue microarrays of nevi, melanoma, and metastatic melanoma showed a decrease in Plexin C1 expression in metastatic melanoma, and an inverse correlation of Plexin C1 expression with depth of invasion. We examined the signaling intermediates of Sema7A and downstream targets of Plexin C1 in human melanocytes. Sema7A activated mitogen-activated protein kinase and inactivated cofilin, an actin-binding protein involved in cell migration. When Plexin C1 expression was silenced, Sema7A failed to phosphorylate cofilin, indicating that cofilin is downstream of Plexin C1. Further, Lim kinase II, a protein that phosphorylates cofilin, is upregulated by Sema7A in a Plexin C1-dependent manner. These data identify Plexin C1 as a potential tumor suppressor protein in melanoma progression, and suggest that loss of Plexin C1 expression may promote melanoma invasion and metastasis through loss of inhibitory signaling on cofilin activation.

Pyoderma faciale.

Pyoderma faciale is a rare cutaneous disorder that predominantly affects women in their 20s and 30s and is characterized by the rapid appearance of coalescing nodules and draining sinuses, combined with livid erythema on the face. We describe a 40-year-old woman who presented with localized pyoderma faciale that worsened during treatment with oral and topical antibiotics and corticosteroids. Subsequent treatment with isotretinoin for 5 months resulted in dramatic and sustained improvement.

Congenital leukemia cutis.

We describe a premature neonate who was born with pancytopenia and a single subcutaneous nodule on her right lower extremity. A biopsy specimen from the nodule demonstrated a dense infiltrate of pleomorphic mononuclear cells that extended throughout the dermis and into the subcutaneous tissue. Immunohistochemical stains and bone marrow examination confirmed a diagnosis of acute myelogenous leukemia. Cytogenetic studies on peripheral blood by G-banding analysis revealed an abnormal karyotype of 46, XX, ins[inv(10)(p11.2q22.2);11](q22.2;q13.2q23.2). A split in the mixed lineage leukemia gene was identified by fluorescence in situ hybridization. Induction chemotherapy was started but was complicated by multiorgan failure. The patient died on the eleventh day of life. As leukemia cutis more typically presents as multiple infiltrative papules, nodules, or plaques, we stress the importance of including leukemia in the differential diagnosis of a solitary nodule in a neonate.

Chronic arsenicism from Chinese herbal medicine.

Chronic arsenicism is associated with cutaneous manifestations, including palmoplantar keratoses, pigmentary anomalies, and nonmelanoma skin cancer. It occurs most commonly following exposure to inorganic arsenic in contaminated drinking water or occupational contact, though medicinal exposure also has been reported. We present a case of a Chinese woman living in the United States with cutaneous manifestations of chronic arsenicism due to a 5-year history of Chinese herbal medicine ingestion.

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCzeta.

Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE(2), a ligand for 4 related G-protein-coupled receptors (EP(1), EP(2), EP(3) and EP(4)). Our previous work established that PGE(2) stimulates melanocyte dendrite formation through activation of the EP(1) and EP(3) receptors. The purpose of the present report is to define the signaling intermediates involved in EP(1)- and EP(3)-dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCzeta isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCzeta activation on EP(1)- and EP(3)-dependent dendrite formation in melanocytes. Stimulation of the EP(1) and EP(3) receptors by selective agonists activated PKCzeta, and inhibition of PKCzeta activation abrogated EP(1)- and EP(3)-receptor-mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP(1) and EP(3) receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP(1,3)-receptor agonists. We show that melanocytes express only the EP(3A1) isoform, but not the EP(3B) receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP(3) agonists. Our data suggest that PKCzeta activation plays a predominant role in regulation of PGE(2)-dependent melanocyte dendricity.

Effects of glimepiride and glyburide on glucose counterregulation and recovery from hypoglycemia.

Severe hypoglycemia, the most serious side effect of sulfonylurea therapy, has been reported to occur more frequently with glyburide than glimepiride. The present studies were undertaken to test the hypothesis that a differential effect on glucagon secretion may be involved. We performed hyperinsulinemic hypoglycemic (approximately 2.5 mmol/L) clamps in 16 healthy volunteers who received in randomized order placebo, glyburide (10 mg), and glimepiride (4 mg) just before beginning the insulin infusion and measured plasma glucagon, insulin, C-peptide, glucagon, epinephrine, cortisol, and growth hormone levels during the clamp and during a 3-hour recovery period after discontinuation of the insulin infusion. Neither sulfonylurea altered glucagon responses or those of other counterregulatory hormones (except cortisol) during the clamp. However, glyburide delayed plasma glucose recovery from hypoglycemia (plasma glucose at end of recovery period: control, 4.9 +/- 0.2 mmol/L; glyburide, 3.7 +/- 0.2 mmol/L; P = .0001; glimepiride, 4.5 +/- 0.2 mmol/L; P = .08). Despite lower plasma glucose levels, glyburide stimulated insulin secretion during this period (0.89 +/- 0.13 vs 1.47 +/- 0.15 pmol x kg(-1) x min(-1), control vs glyburide; P = .001), whereas glimepiride did not (P = .08). Short-term administration of glyburide or glimepiride did not alter glucagon responses during hypoglycemia. In contrast, during recovery from hypoglycemia, glyburide but not glimepiride inappropriately stimulates insulin secretion at low plasma glucose levels. This differential effect on insulin secretion may be an important factor in explaining why glyburide causes severe hypoglycemia more frequently than glimepiride.