Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen.

Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor.

Moles and site-specific risk of nonfamilial cutaneous malignant melanoma in women.

We examined the relationship between self-reported mole counts and cutaneous melanoma with respect to anatomic site in 110 case and 231 control female nurses. Counts of moles on the lower leg were better predictors of melanoma risk than were counts of moles on the arm. The relative risk for the highest quintile of lower leg mole counts versus no lower leg moles was 4.2. Mole counts at each site (arm, thigh, and lower leg) were associated with risk of melanoma of the trunk and lower leg, but none were associated with the risk of melanoma of the upper extremity. The absence of direct site-specificity suggests that mole counts primarily indicate systemic melanoma risk, rather than direct risk from the moles themselves.

Histologic comparison of argon and tunable dye lasers in the treatment of tattoos.

Cosmetic benefit from laser therapy of tattoos may simply be the result of thermal injury and host reparative response which remove pigment by a "slough and bury" mechanism. Tattoo pigment of 4 colors (black, white, red, and blue) was introduced into the skin of guinea pigs and studied histologically at 48 h, 7 days, 4 and 6 weeks, and 3 months. Tattoos of each color were treated with argon laser (488 and 514 nm) and tunable dye laser at 3 different wavelengths (505, 577, and 690 nm). Treated tattoos were biopsied immediately and at 48 h, 7 days, and 3 months. Selective laser absorption by the tattoo pigment was suggested by pigment-related differences in threshold doses for histologic damage. Clinical clearing of tattoo pigment correlated well with the extent of immediate epidermal and dermal necrosis and was as well associated histologically with the deposition of parallel bands of collagen fibers (i.e., scar) between the residual pigment and the overlying epidermis. "Lightening" of tattoos probably depends more on widespread necrosis, subsequent tissue sloughing, and resultant dermal fibrosis than on specific changes in tattoo pigment chemistry, morphology, physical properties, or handling by macrophages.

Ultrastructural documentation of HLA-DR antigen reactivity in normal human acrosyringial epithelium.

We have observed that monoclonal antibodies directed against human Ia-like antigens react with a subset of epidermal keratinocytes as well as Langerhans cells in normal human skin. Membrane reactivity for HLA-DR antigen in flattened ductal keratinocytes and in adjacent cuticular cells forming the acrosyringial lumen was observed using immunoelectron microscopy. It should be recognized that Ia-positive acrosyringial keratinocytes represent a potential source of contamination in methods designed to study and isolate Langerhans cells using antibodies directed against HLA-DR antigens. Teleologic considerations of HLA-DR antigen expression in the acrosyringium are discussed.

Location of HLA-A,B,C antigens in dendritic cells of normal human skin: an immunoelectron microscopic study.

The distribution of the major histocompatibility antigens HLA-A,B,C, (HLA) on dendritic cells of normal human skin was studied by immunoelectron microscopy and a 4-step immunoperoxidase technique utilizing monoclonal antibodies. Light microscopy revealed peripheral staining for HLA of epidermal and pilar infundibular keratinocytes. In the epidermis, the staining was present from the basal layer to the upper stratum spinosum. In the follicles below the level of the infundibulum, HLA was detected only on rare intraepithelial dendritic cells. These dendritic cells could not be identified in the epidermis due to the HLA staining of the surrounding keratinocytes. Similar cells stained diffusely with anti-T6 antibody; the keratinocytes did not. Immunoelectron microscopy demonstrated: (1) the presence of HLA staining of keratinocyte membranes from the stratum basalis to the level of the upper stratum spinosum and in the pilar infundibulum, (2) the possible absence of HLA on melanocytes, (3) the presence of focal HLA staining of the membranes of epidermal and follicular dendritic cells that contained Birbeck granules and were, therefore, Langerhans cells, (4) dendritic mononuclear cells within the follicular epithelium, which although devoid of Birbeck granules, exhibited similar reactivity with anti-HLA antibody. These findings suggest that HLA antigens are present on the membranes of Langerhans cells, but are not demonstrable on melanocytes in normal human skin.

Nonfamilial cutaneous melanoma incidence in women associated with sun exposure before 20 years of age.

Despite strong evidence that sun exposure causes malignant melanoma, the details of this relation remain unclear. A nested case-control analysis was conducted within the Nurses' Health Study cohort to examine the relation between timing of severe sun exposure and incidence of melanoma. The subjects were 130 white women aged 38 to 65 years with confirmed cutaneous melanoma (other than acral lentigenous) who reported no history of melanoma in first-degree relatives. The control subjects were 300 women matched by race, date of birth, and cycle of questionnaire who also reported no history of melanoma in first-degree relatives. We used conditional logistic regression to evaluate the relation of sun damage after 30 years of age and sun damage from 15 to 20 years of age to the incidence of melanoma. Blistering sunburns between 15 to 20 years of age were associated with risk of melanoma (relative risk = 2.2 for five or more burns vs none, 95% confidence interval 1.2 to 3.8). This association persisted when a history of burns after 30 years of age was controlled in the analysis. No material association was found between blistering sunburns after 30 years of age and melanoma. Similarly, a more equatorial latitude of residence between 15 and 20 years of age was positively associated with melanoma; latitude after 30 years of age was less strongly and not significantly related to melanoma risk. Sun exposure prior to 20 years of age is more closely associated with melanoma risk than sun exposure after 30 years of age.

Human cutaneous dendritic cells express two glycoproteins T6 and M241 which are biochemically identical to those found on cortical thymocytes.

Monoclonal antibodies anti-T6 and anti-M241 define unique cell populations within different lineages: cortical thymocytes and dendritic cells in the skin. T6 positive cutaneous dendritic cells are located predominantly in the epidermis and belong to the Langerhans/indeterminate lineage, whereas, most of the M241 positive cells are located in the perivascular regions of the dermis. Biochemical analysis of thymocytes and cutaneous dendritic cells was performed in order to determine whether the reactivity of these antibodies with these cell types is due to sharing of antigenic determinants by two unrelated proteins, or whether similar proteins are present on cells of different lineages. Our results indicate that T6 antigens are borne by the same glycoprotein (49K) on cortical thymocytes and Langerhans/indeterminate cells. Similarly, M241 antigens isolated from thymocytes and cutaneous dendritic cells are found on the same glycoprotein (43K).

Desipramine and cutaneous reactions in pediatric outpatients.

The association of adverse cutaneous effects with administration of the tricyclic antidepressant drug desipramine was systematically reviewed in a clinic population of 205 child psychiatry outpatients over a 3-year period. Transient maculopapular rashes developed in 12 children and adolescents treated with desipramine. The rashes had a benign course, disappearing completely in 2 to 7 days, and were not associated with clinical or chemical hepatitis or any other physical symptoms.

Ichthyosiform dermatosis and deafness. Report of a case and review of the literature.

A patient suffering from an ichthyosiform dermatosis, partial deafness, and pes cavus is described. Most of the body surface was covered by fine white scales; red scaling plaques were present on the arms. There were slight hyperkeratoses of the palms and soles, keratosis pilarislike lesions with perifollicular redness on the trunk, and multifocal alopecia. A biopsy specimen of the scaly erythematous plaque demonstrated hyperkeratosis with follicular plugging, papillomatosis, and acanthosis. Direct immunofluorescence studies of lesional skin using monoclonal antibodies to epidermal prekeratin, filaggrin, and involucrin revealed normal staining patterns. The patient's cultured keratinocytes were morphologically unremarkable and contained profilaggrin, involucrin, and a normal complement of cytokeratins. The expression of the disease may not occur in cultured cells, because they lack many features of fully keratinized cells. A review of the literature concerning ichthyosis and deafness reveals that the constellation of cutaneous and extracutaneous abnormalities in this case does not exactly conform to that in previously reported cases. Precise classification of the patient's disorder will require demonstration of the basic defect(s).

Multiple cutaneous melanoma metastases of an extremity resembling Kaposi's sarcoma: use of regional perfusion.

We report on a patient with primary cutaneous malignant melanoma, with numerous intransit metastases involving the left lower extremity. The clinical presentation was striking in that the intransit metastatic lesions of the skin had morphologic characteristics of Kaposi's sarcoma. Her disease was complicated by marked lower limb edema. Cutaneous ulceration did not develop despite the extensive tumor burden. Treatment with regional limb perfusion resulted in marked reduction of the edema and shrinkage of the tumor mass. In addition to presenting this case report and response to therapy, we would like to suggest the term "chronic melanoma of the extremity" (CME) as a descriptive term for this unusual variant of malignant melanoma.

Delayed and persistent cutaneous reactions to coelenterates.

Three patients are described who developed firm, persistent papules and plaques at sites of previous contact with two species of coelenterates. Histologically, a predominantly mononuclear inflammatory cell infiltrate located primarily in the reticular dermis was observed with destruction of hair follicle epithelium and arrectores pilorum. Epidermal changes included focal spongiosis and exocytosis of lymphocytes. The eruptions subsided no sooner than 7 weeks from time of onset. It is hypothesized that this cutaneous reaction represents a persistent delayed hypersensitivity response to an antigenic component of the coelenterate nematocyst.

Hereditary callosities with blisters. Report of a family and review.

A family with calluses of the soles associated with blistering is described. Electron microscopic study of a bulla showed an intraepidermal blister with cytolysis of keratinocytes and clumping of tonofilaments. Review of the literature and our own experience with keratoderma palmaris et plantaris revealed no similar patients with this combination of findings. The appearance of the soles is similar to pachyonychia congenita, but the lack of nail and mucous membrane changes is not consistent with that disorder. Treatment with isotretinoin caused reduction in the size of the calluses but exacerbated the blistering.

Ultrastructural documentation of M241 glycoprotein on dendritic and endothelial cells in normal human skin.

M241 is a glycoprotein that recently has been demonstrated to be present in human thymus in a distribution similar to T6. Studies in skin, however, suggest that M241, in contrast to T6, is detected only on a subset of Langerhans cells and on a population of dendritic cells in the superficial dermis. We compared the reactivities of monoclonal antibodies to M241 and T6 with dendritic cells in normal human skin using immunoelectron microscopy. Our findings indicate that M241 is present on a minority of Langerhans cells and on a substantial number of other predominantly dermal dendritic cells with morphologic features of indeterminate cells. Anti-M241 reactivity was generally restricted to the cell membrane, although cytoplasmic reactivity was detected in some Langerhans cells. Dermal endothelial cells, which like dendritic cells are capable of antigen presentation, were also reactive with anti-M241 antibody. M241 is a glycoprotein, different from T6, with a tissue distribution potentially relevant to the understanding of antigen-presenting cells in the skin.

Follicular mucinosis: a detailed morphologic and immunopathologic study.

Two patients with the benign type of follicular mucinosis (FM) are presented. Their clinical features and course were characteristic for this subgroup of FM. Light and electron microscopy, direct immunofluorescence, and immunoperoxidase cell marker studies were undertaken to characterize the nature of the disease process. Light microscopy confirmed the follicular outer root sheath and sebaceous gland epithelial degenerative changes. The infiltrating inflammatory cells were morphologically benign. Electron microscopy detailed the cellular associations in the areas of degenerative change. Disattached keratinocytes were closely apposed to significant numbers of macrophages and Langerhans cells. Direct immunofluorescence studies demonstrated primarily complement (C3) and fibrinogen/fibrin in areas of reticular degeneration. Immunoperoxidase studies revealed large numbers of T cells and macrophages and a striking increase in the number of Langerhans cells in the affected follicular epithelium. The findings suggest that cell-mediated immune mechanisms may play a role in the pathogenesis of this disorder.

Intermittent hair follicle dystrophy. Report of a new disorder.

A new disorder of the hair follicle is described that leads to increased fragility of the shaft. Light microscopic studies of hair follicles revealed disturbances of keratinization in the shafts that are very likely responsible for the breakage. The most consistent change seen by transmission electron microscopy was intercellular edema of the outer root sheath, while scanning electron microscopy of the hair revealed disturbances of the surface and broken ends. Specific biochemical abnormalities of the hair proteins were not found. Possible mechanisms for the disease are discussed.

Prognosis for polypoidal melanoma is determined by primary tumor thickness.

Survival of 23 patients with polypoidal malignant melanomas was compared with an identical number of patients with nonpolypoidal melanomas of similar thickness, stage, and location. Five-year survivals for the two groups were not significantly different. The dominant prognostic factor leading to the adverse prognosis associated with polypoidal melanomas was the primary tumor thickness (all greater than 1.70 mm) and not the polypoidal morphologic configuration per se.

Circulating CEA levels in patients with fulminant hepatitis.

CEA levels were determined in blood specimens from 14 persons suffering from fulminant hepatitis. Values ranged from 1.9 to 21 ng/ml with a mean of 7.0 ng/ml. All except one patient had a CEA level greater than 2.5 ng/ml, but only three exceeded 10 ng/ml. There was no correlation between single CEA levels and prognosis, routine liver chemistries, or histopathologic characterization of hepatic tissue obtained at postmortem examination. These data show that patients with fulminant hepatitis commonly had increased circulating levels of CEA, but these elevations were far less than may be found in patients with hepatic metastases. In severe hepatic dysfunction reduced hepatic clearance of CEA may be responsible for the increased levels.

Selective vascular coagulation of rabbit colon using a flashlamp-excited dye laser operating at 577 nanometers.

Previous studies have demonstrated that brief pulses of selectively absorbed optical radiation can be used to confine thermal injury to pigmented targets within tissues. We performed studies in rabbits to assess the usefulness of this technique for selectively coagulating the colonic vasculature. By measuring the optical absorbance of rabbit colon with a spectrophotometer, it was determined that hemoglobin exhibits strong absorption relative to the rabbit colon at a wavelength of 577 nm. Because light must be absorbed to affect tissue, it was hypothesized that laser pulses of this wavelength would selectively damage blood vessels. This hypothesis was tested by examining the effect of 300-microseconds-long 577-nm laser pulses on rabbit colon in vivo. For delivered radiant exposures between 4 and 8 J/cm2, selective coagulation of the colonic vasculature could be produced without damage to the surrounding colon. At greater radiant exposures, vessel hemorrhage was occasionally noted but no transmural thermal injury was produced with delivered radiant exposures as high as 22 J/cm2. This technique may form the basis of a safe and simple treatment of vascular lesions of the colon such as angiodysplasia.