Inhibition of growth of B16 murine malignant melanoma by exogenous interferon.

We previously reported that polyinosinic-polycytidylic acid, a potent interferon inducer, inhibits the growth of B16 malignant melanoma in the C57BL/6 mouse. Two experiments were done to evaluate the effectiveness of interferon in tumor inhibition in vivo. In the first, mice were implanted with melanoma and divided into four groups, according to treatment: interferon preparation; interferon control preparation ("breakthrough fraction"); phosphate-buffered saline control; and murine serum albumin control. Daily, each mouse was given i.p. injections of 200,000 NIH reference units (hereafter called units) of interferon or of one of the control substances. The second experiment was similar to the first, except that bovine serum albumin was an additional control. In both experiments, the average tumor volume in interferon-treated mice was statistically significantly smaller than that of each control group. Mouse interferon preparations also inhibited the multiplication of B16 malignant melanoma cells in culture. This inhibition was statistically significant from interferon levels as low as 5 to as high as 5000 units/ml. The degree of inhibition markedly increased from 5 up to 500 units, the inhibition reaching its maximum at this concentration. The inhibitory effect of interferon was abrogated by anti-murine interferon serum produced in a rabbit. These findings suggest that the in vivo inhibition of the growth of B16 melanoma demonstrated with polyinosinicpolycytidylic acid and with exogenous interferon probably results, at least in part, from a direct effect of interferon on the tumor cells themselves.

Distribution of technetium-99m sulfur colloid in mice bearing melanomas or mammary carcinomas.

Three groups of 24 C57BL/6J black mice were studied. One group was implanted with B16 malignant melanoma, another was implanted with mammary adenocarcinoma, and the third was not given tumor implants. After 14 to 17 days, the mice were given injections i.v. of technetium-99m sulfur colloid and killed 30 min later. Organs were weighed, and radioactivity was counted. The ratios of specific radioactivities of the spleens to those of the liver were higher only in the group of mice bearing malignant melanomas. This finding suggests that the "hot spleen" phenomenon observed in humans with malignant melanomas may be due to increased specific activity rather than increased splenic volume.

Prognosis of clinical stage I melanoma patients with positive elective regional node dissection.

We tested 12 clinical and histologic variables to see which ones best predicted death from melanoma in 66 patients with positive elective regional node dissections (clinical stage I, pathologic stage II [CSI, PSII]). Despite the presence of lymph node metastases, not all patients had poor prognoses. Patients with tumors less than or equal to 3.5 mm and a percentage of positive nodes less than or equal to 20% had a 7-year survival rate of 66%. Within this low-risk group the subset with primary lesions on the trunk or extremities (except hands and feet) had a 7-year survival rate of 76%. This compares with poor 7-year survivals of 29% and 30% observed in other defined high-risk groups. Our results confirm and extend earlier observations concerning the prognoses of CSI, PSII melanoma patients and are relevant to any ongoing and future studies concerning elective regional node dissection (ERND) or adjuvant therapy trials in melanoma.

Lentigo maligna melanoma has no better prognosis than other types of melanoma.

We studied 48 patients with lentigo maligna melanoma (LMM) and compared the clinical stage I patients with non-LMM melanoma patients (matched by site and thickness) to see if prognosis differed. There was no significant difference in mortality from melanoma between the two groups (P = .68) after a mean follow-up time of five years (67.5 months for LMM, 60.5 months for non-LMM). In addition, a Cox multivariate analysis of the entire matched group showed that only thickness was significantly associated with death from melanoma (P = .0007) while histology (LMM v non-LMM) did not make a significant contribution (P = .61). Our data suggest that after accounting for primary tumor thickness and site, LMM and non-LMM have the same prognosis and biologic behavior, in contrast to the widely held belief that LMM has a better prognosis than other forms of melanoma.

Retention of antimelanoma effect of polyinosinic-polycytidylic acid in neonatally thymectomized, irradiated, leukopenic mice.

Polyinosinic-polycytidylic acid (PIC), a synthetic polyribonucleotide, inhibits the growth of B16 malignant melanoma in C57BL/6 mice. Since PIC has been reported to augment immune responses, we tested the hypothesis that the antitumor effect of PIC against B16 melanoma is via immune stimulation. Mice were neonatally thymectomized or neonatally thymectomized and subsequently irradiated to suppress their immune reactivity. In such animals PIC retained its ability to inhibit the growth of B16 melanoma, in the face of profound leukopenia and lymphopenia, suggesting that its antimelanoma effect is probably not mediated by augmentation of the host's immune antitumor response.

Early death from clinical stage I melanoma.

We studied 13 prognostic factors in 582 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma within the first 24 months following diagnosis. Thirty-six patients died during this period. Only 2 deaths occurred in patients with primary tumors thinner than 1.70 mm, and only 2 patients of 189 died with tumors located on the non-BANS extremities, excluding the hands and feet. Individual factors associated with high risk for death within 2 years included level V tumors, acral location, thickness greater than or equal to 3.65 mm, histologic ulceration greater than 3 mm, nodular type, presence of microscopic satellites, greater than 6 mitoses/mm(2), positive elective node dissection, absence of lymphocyte response at the tumor base, and absence of an associated nevus histologically. Many of the preceding individual factors are highly correlated. By the use of logistic regression analysis, only one very high risk group was found: 71 percent of patients with level V tumors greater than 1.70 mm thick with histologic ulceration width greater than 3 mm located in an area other than the extremities (excluding hands and feet) had died within 2 years of diagnosis. The ability to select high-risk groups should be useful to investigators involved with the design and evaluation of adjuvant therapy studies.

Factors associated with death from melanoma from 2 to 5 years following diagnosis in clinical stage I patients.

We studied 14 prognostic factors in 428 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma from 24 to 60 months following diagnosis. Forty-eight patients (11 percent) died during this period. All 17 patients who had visceral metastases present at 24 months died during this period. All surviving patients were followed for at least 60 months. Individual high risk factors included ulceration width (as determined by histology), level IV or V tumor, recurrence other than visceral, 6 or more mitoses per square millimeter, presence of involved nodes on elective dissection, absent or slight lymphocyte response, tumor type other than superficial spreading, location other than extremities (excluding hands and feet), microscopic satellites, thickness, sex, and wide local excision. The presence of sex as a risk factor for patients dying from 2 to 5 years following diagnosis is noteworthy because no sex difference was noted in the early death (<24 months) group. Age, presence of a nevus, and histologic regression were not significant factors. A logistic regression analysis selected a combination of the following independent factors: (1) location on extremities excluding hands and feet (favorable), (2) thickness, (3) recurrence other than visceral, (4) positive elective nodal dissection, (5) 6 or more mitoses per square millimeter, and (6) moderate to marked lymphocyte response (favorable). Twenty-five percent of patients with level IV lesions died between 24 and 60 months compared with only a 6 percent death rate within the first 24 months.

Early death from clinical stage I melanoma.

We studied 13 prognostic factors in 582 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma within the first 24 months following diagnosis. Thirty-six patients died during this period. Only 2 deaths occurred in patients with primary tumors thinner than 1.70 mm, and only 2 patients of 189 died with tumors located on the non-BANS extremities, excluding the hands and feet. Individual factors associated with high risk for death within 2 years included level V tumors, acral location, thickness greater than or equal to 3.65 mm, histologic ulceration greater than 3 mm, nodular type, presence of microscopic satellites, greater than 6 mitoses/mm2, positive elective node dissection, absence of lymphocyte response at the tumor base, and absence of an associated nevus histologically. Many of the preceding individual factors are highly correlated. By the use of logistic regression analysis, only one very high risk group was found: 71 percent of patients with level V tumors greater than 1.70 mm thick with histologic ulceration width greater than 3 mm located in an area other than the extremities (excluding hands and feet) had died within 2 years of diagnosis. The ability to select high-risk groups should be useful to investigators involved with the design and evaluation of adjuvant therapy studies.

Factors associated with death from melanoma from 2 to 5 years following diagnosis in clinical stage I patients.

We studied 14 prognostic factors in 428 patients with clinical stage I melanoma to determine which factor or combination of factors was associated with death from melanoma from 24 to 60 months following diagnosis. Forty-eight patients (11 percent) died during this period. All 17 patients who had visceral metastases present at 24 months died during this period. All surviving patients were followed for at least 60 months. Individual high risk factors included ulceration width (as determined by histology), level IV or V tumor, recurrence other than visceral, 6 or more mitoses per square millimeter, presence of involved nodes on elective dissection, absent or slight lymphocyte response, tumor type other than superficial spreading, location other than extremities (excluding hands and feet), microscopic satellites, thickness, sex, and wide local excision. The presence of sex as a risk factor for patients dying from 2 to 5 years following diagnosis is noteworthy because no sex difference was noted in the early death (less than 24 months) group. Age, presence of a nevus, and histologic regression were not significant factors. A logistic regression analysis selected a combination of the following independent factors: (1) location on extremities excluding hands and feet (favorable), (2) thickness, (3) recurrence other than visceral, (4) positive elective nodal dissection, (5) 6 or more mitoses per square millimeter, and (6) moderate to marked lymphocyte response (favorable). Twenty-five percent of patients with level IV lesions died between 24 and 60 months compared with only a 6 percent death rate within the first 24 months.

A prognostic model for clinical stage I melanoma of the lower extremity. Location on foot as independent risk factor for recurrent disease.

Thirteen variables were studied to determine their usefulness in predicting recurrent disease in 158 patients with stage I melanoma of the lower extremity. A Cox proportional hazards analysis demonstrated that three variables were independent risk factors for recurrent disease in these patients: (1) thickness, in millimeters, of the primary tumor (P = 0.000009), (2) primary tumor location on the foot (P = 0.0003), and (3) the number of mitoses/mm2 (P = 0.0244). Life-table analyses of patient subgroups defined by different combinations of these three variables demonstrated that thick (greater than or equal to 3.0 mm) melanomas of the foot were associated with recurrent disease much more frequently than tumors of similar thickness located on the thigh or calf. These data provide guidelines that can be used to evaluate results of surgical and/or adjuvant therapy studies for patients with melanoma of the lower extremity.

Familial multiple desmoplastic trichoepitheliomas.

A kindred with familial multiple desmoplastic trichoepitheliomas is described. Desmoplastic trichoepitheliomas should be added to the group of lesions that indicate an inherited pattern when they occur as multiple primary tumors. The implications for nosologic status and treatment of desmoplastic trichoepitheliomas are considered.

Multivariate risk score for recurrence of cutaneous basal cell carcinomas.

Multiple logistic analysis relating prognostic factors to risk of recurrence was performed for 1,417 basal cell carcinomas treated from 1955 to 1969 at New York University. The overall five-year recurrence rates by therapy were as follows: curettage-electrodesiccation, 26.0% (197/758); x-ray therapy, 9.7% (40/412); and surgical excision, 9.3% (23/247). Results for each treatment subgroup indicated that increasing lesion diameter and location of the lesion on various sites of the head, especially the nose, were associated with an increased risk of recurrence, whereas lesion location on the neck, trunk, limbs, or genitalia was associated with a decreased risk of recurrence. Additional significant factors correlated with increased risk were as follows: among patients treated with x-irradiation, male sex, and, among those treated by curettage-electrodesiccation, prior therapy and increasing patient age.

Total-body photographs of dysplastic nevi.

A method of taking total-body photographs to document dysplastic nevi is described. A set of 24 views is taken. These 35-mm color slide transparencies are projected onto a rearview screen at the time of subsequent follow-up examinations. A comparison between the baseline photographs and the current clinical findings allows the physician to detect thin malignant melanomas in a curable stage.

Diagnostic accuracy in malignant melanoma.

The diagnostic accuracy and index of suspicion concerning malignant melanoma were calculated based on review of 5,538 histologically examined lesions (of which 99 were melanomas) that were recorded in the Oncology Section of the Skin and Cancer Unit from 1955 to 1967. The diagnostic accuracy of the physicians in the Section was determined to be 64.4%. Thus, in almost one of every three melanomas an error in clinical diagnosis was made. This "batting average" is, however, better than those of previously published reports. The index of suspicion in relation to malignant melanoma in our series was 96%. Thus, the physicians in the Oncology Section demonstrated an appropriate awareness of this tumor. However, coupled with a diagnostic accuracy of 64%, a problem nevertheless exists in the diagnosis of this serious cutaneous cancer. Our study emphasizes the importance of having histologic verification prior to definitive radical surgery on patients with malignant melanoma.

DermLit. A year's experience with a computerized literature search service.

DermLit is a service providing bibliographies prepared by computer from a file of the four basic English language dermatology journals beginning with January 1969 and including the current issues. An abstract of each article cited is returned with the report. Both the title and the abstract of each article in the file is searched for the word, words, or phrases requested by the user. In the year since DermLit was introduced, more than 1,600 searches have been performed for dermatiologists all over the United States and Canada. The service is used primarily by dermatologists away from the large teaching centers. The topics of the search requests cover the entire field of dermatology.

Bowenoid papulosis of the genitalia.

We report 34 cases of bowenoid papulosis of the genitalia. In each case, the patient had numerous reddish brown or violaceous papular lesions, some distinctly verrucoid, situated on the genitalia. Although clinically the lesions invariably appeared benign, histologic examination of specimens from the genital lesions in each patient showed changes of squamous cell carcinoma in situ. Many of the patients gave a history of preceding viral lesions on the genitalia. Therapy in all cases was conservative but thoroughly ablative. We view bowenoid papulosis as a new entity whose biologic behavior if untreated is as yet unknown.

Treatment of morphea-type basal cell carcinomas with radiation therapy.

Eight patients received superficial x-ray therapy for morphea-type basal cell carcinomas. Seven lesions did not recur. One recurrence adjacent to an irradiated field was observed; it was considered to be a geographic miss and has led us to include a wider field (10 mm) of normal-appearing skin beyond the clinical perimeter of the tumor when the lesion is ill-defined. The cosmetic results after treatment were poorer than anticipated for this schedule of radiation therapy, based on our extensive experience with other types of basal cell carcinomas. To obtain the best long-term results we believe that, where technically feasible Mohs surgery and conventional surgical excision with histologic verification of free margins are the treatments of choice for morphea-type basal cell carcinomas. However, our experience indicates that morphea-type basal-cell carcinomas can be cured with radiation therapy; therefore, x-rays have a place in the armamentarium of therapeutic modalities for this tumor if surgery is not feasible or if it is refused by the patient.

Treatment of melanotic freckle with x-rays.

Sixteen patients were treated for melanotic freckle of Hutchinson (lentigo maligna) with the Miescher technique of x-ray therapy. Eleven patients had no local cutaneous recurrences of persistence following x-ray therapy. Five patients had local recurrence or persistence of their lesions. Three patients developed metastatic malignant melanoma. The first of these three patients had lentigo maligna melanoma, and the second patient had a melanotic freckle with atypical cells extending down the adnexae, including the sweat apparatus to the level of the coiled portion of one sweat gland. The third patient was considered to be in a precancerous phase at the time of irradiation. Nevertheless, metastases occurred. European colleagues indicate that they have not experienced such problems in using the Miescher technique. The procedure has been abandoned in our department, pending further clarification of the discrepancy between our results and those reported by our European colleagues.

Eruptive nevocytic nevi after severe bullous disease.

In two patients, hundreds of nevocytic nevi (melanocytic nevi) appeared in sites of severe bullous dermatoses that were considered to be toxic epidermal necrolysis and erythema multiforme exudativum, respectively. This phenomenon may result from benign melanocytic hyperplasia accompanying keratinocytic hyperplasia during the healing process of some of the denuded areas of the skin.

Surface microscopy of pigmented basal cell carcinoma.

OBJECTIVES: To describe the relevant morphologic features and to create a simple diagnostic method for pigmented basal cell carcinoma (BCC) using in vivo cutaneous surface microscopy (ie, dermoscopy, dermatoscopy, or oil epiluminescence microscopy). DESIGN: Pigmented skin lesions were photographed in vivo using immersion oil (surface microscopy). All pigmented skin lesions were excised and reviewed for histological diagnosis. Photographs of 142 pigmented BCCs, 142 invasive melanomas, and 142 benign pigmented skin lesions were randomly divided into 2 equally sized training and test sets. Images from the training set were scored for 45 surface microscopy features. From this a model was derived and tested on the independent test set. SETTING: All patients were recruited from the primary case and referral centers of the Sydney Melanoma Unit, Sydney, Australia, and the Skin and Cancer Unit, Skin and Cancer Associates, Plantation, Fla. PATIENTS: A random sample (selected from a larger database) of patients whose lesions were excised. MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of pigmented BCCs. RESULTS: The following model was created. For a pigmented BCC to be diagnosed it must not have the negative feature of a pigment network and must have 1 or more of the following 6 positive features: large gray-blue ovoid nests, multiple gray-blue globules, maple leaflike areas, spoke wheel areas, ulceration, and arborizing "treelike" telangiectasia. On an independent test set the model had a sensitivity of 97% for the diagnosis of pigmented BCCs and a specificity of 93% for the invasive melanoma set and 92% for the benign pigmented skin lesion set. CONCLUSION: A robust surface microscopy method is described that allows the diagnosis of pigmented BCCs from invasive melanomas and benign pigmented skin lesions. Arch Dermatol. 2000;136:1012-1016