Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.

AIM: To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). MATERIALS AND METHODS: Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. RESULTS: No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). CONCLUSION: In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts.

Disseminated tumour cells in the bone marrow in early breast cancer: morphological categories of immunocytochemically positive cells have different impact on clinical outcome.

Detection of disseminated tumour cells (DTCs) in bone marrow by immunocytochemistry (ICC) includes morphological evaluation of cytokeratin immunopositive cells. The aim of this study was to disclose the prognostic significance of different morphological categories of ICC-positive cells according to treatment status and tumour subtype. Bone marrow samples (at surgery) were analysed for the presence of cytokeratin-positive DTCs by a standard immunocytochemical method. The immunopositive cells were classified into the following categories, prior to any analysis of the association between DTCs and clinical outcome: tumour cells (TC), uninterpretable cells (UIC), hematopoietic cells (HC), and questionable HC (QHC). The analysis included 747 early breast cancer patients. Median follow-up was 84 months for relapse, and 99 months for death. The categorisation of the ICC positive cells revealed TC in 13.3 % of the patients, whereas 13.1, 17.8, and 21.4 % of the cases were positive for UIC, QHC, and HC, respectively. Analysing all patients, only TC and UIC predicted systemic relapse. Separate analysis of all patients not receiving adjuvant systemic treatment (No-Adj; n = 389) showed that only QHC were associated with reduced survival (DDFS: p = 0.008; BCSS: p = 0.004, log rank) and the presence of QHC also remained significant in multivariate analysis. Primary tumour subgroup analysis (of all patients) by hormone receptors (HR) and HER2, demonstrated that only TC/UIC had prognostic impact in the HR+/HER2- patients, whereas presence of QHC was associated with unfavourable outcome only in triple negative patients (DDFS: p = 0.004; BCSS: p = 0.024). Patients with ≥3HC had improved outcome compared to those with fewer/no HC (DDFS: p = 0.005; BCSS: p = 0.009). Hence, morphological DTC subgroups may differ in clinical significance according to primary tumour subtype and treatment status. This emphasises the importance of DTC characterisation, and separate analyses of DTC categories according to tumour subtype. Hematopoietic ("false positive") cells might predict an immune-related favorable clinical outcome.

Locally recurrent malignant melanoma characteristics and outcomes: a single-institution study.

Despite improvements in the identification and treatment of melanoma, local recurrence continues to challenge the success of current melanoma therapy. A retrospective analysis of 1,996 patients presenting from 1990 to 1997 at the Pigmented Lesion Group of the University of Pennsylvania was performed to assess clinical characteristics and outcomes of locally recurrent melanoma. The cases were analyzed by chart and pathological slide review. A control group was identified for statistical comparison. The incidence of locally recurrent melanoma during the study period was 2.2%. Lentigo maligna melanoma (LMM) accounted for 37% of the local recurrences. Increased tumor thickness and microsatellites were associated with "early" local recurrence and decreased survival from time of recurrence. Nineteen percent of the local recurrences occurred more than 5 years after the initial definitive treatment. The preponderance of locally recurrent LMM suggests the need for refinements in the techniques of margin identification and surgical excision of LMM. Tumors with increased thickness and microsatellites should receive particularly close attention. Lastly, with nearly 20% of the local recurrences occurring more than 5 years after the initial date of treatment, the authors suggest extending the follow-up time for all melanoma lesions beyond 5 years.

Signs and symptoms of melanoma in older populations.

We conducted a descriptive study to assess the relationship between increasing age and the reporting of melanoma signs/symptoms in 634 hospital-based and 624 population-based incident cases of melanoma. Multivariate logistic regression was used to evaluate the relationship between older age (> or = 50 years) and the reporting of melanoma signs/symptoms. Older patients were less likely to report itching and change in elevation of their lesions (P < 0.05). Change in color was also less likely to be reported by older patients, although not statistically significant. Ulceration of the lesion was reported significantly more by older patients (P < 0.05). Older individuals may be less likely to report itching and change in elevation/color of their lesions, but more likely to report ulceration, a symptom associated with advanced disease and poor prognosis. Further research is necessary to provide a better understanding of the development of melanoma in older populations so that new strategies can be explored to improve early detection in this age group.

Hormonal influences on women with psoriasis.

Various endogenous factors such as stress and infection are known to influence psoriasis. Previous data suggest that pregnancy has a significant influence on the course of psoriasis. This study explores the effect of pregnancy as well as other hormonal events on psoriasis in women.

Melanoma of unknown primary site: presentation, treatment, and prognosis--a single institution study. University of Pennsylvania Pigmented Lesion Study Group.

BACKGROUND: A retrospective analysis of 40 patients diagnosed with melanoma of unknown primary site (MUP) was undertaken to analyze the etiology and clinical behavior of this presentation. METHODS: The patient records were located by a computer search of the Pigmented Lesion Clinic data base at the University of Pennsylvania. With the Cox proportional hazards model, the survival of the MUP patients with lymph node presentation was compared with that of patients with lymph node disease and a known concurrent primary melanoma. RESULTS: Sixty-five percent of the patients presented with lymph node metastasis only, 28% presented with visceral lesions, and 8% presented with subcutaneous nodules. The prevalence of dysplastic nevi was 22.5%. The overall 4-year survival rate for the 40 MUP patients was 55% +/- 9%. The 4-year survival (57% +/- 12%) of patients with lymph node presentation was compared with that of patients presenting with lymph node disease and a known concurrent primary melanoma (19 +/- 6%). Survival was significantly different between the groups (P = 0.008). This survival difference remained significant (P = 0.02) even after adjustments for number of positive lymph nodes, year of diagnosis, and age at diagnosis. CONCLUSIONS: This analysis revealed that MUP patients with lymph node metastasis survived significantly longer than patients diagnosed with lymph node metastasis concurrent with a known cutaneous primary melanoma. The prevalence of dysplastic nevi in the MUP patient series was intermediate between that reported among primary melanoma patients and that reported among population controls, suggesting the likelihood of a primary cutaneous origin for the metastatic melanoma.

[Colorectal cancer. Location dependent symptoms?]. / Kolorektalcancer. Lokalisasjonsavhengige symptomer?

It is claimed that the symptoms of cancer in different parts of the colorectum are varied. The aim of the study was to decide how well the "classical" symptoms are divided between left and right colonic and rectal adenocarcinomas. This was a retrospective study of 102 patients with colorectal cancer at Ullevål hospital in 1992. Red blood in the faeces (p = 0.001), and changes in stool pattern (p = 0.001), were left colonic and rectal cancer specific. Moreover tenesmus, mucous stools, and pain at defecation were specific of rectal cancer. All these findings agree with the textbooks. Melaena, diarrhoea (p = 0.23), weight-loss (p = 0.09), a feeling of general physical weakness (p = 0.13), and ileus/subileus were not found as localisation specific symptoms, contrary to the claims of several textbooks. Pain was always correlated to the affected side in left and right colonic cancer, while in rectal cancer the localisation of pain was non-specific, and it appeared rather often; (37%) in Dukes' A and Dukes' B. Only a few patients had anorexia, but the number was still significant for those with right colonic cancer (p = 0.04). With few exceptions, our results generally support the textbooks. The referring symptoms may help to decide the necessity for further examinations, when total colonoscopy is not obtained.

A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group.

OBJECTIVE: To develop a prognostic model, based on clinical and pathologic data that are routinely available to the clinician, that would estimate the chance for survival of a patient with primary cutaneous melanoma after definitive surgical therapy. DESIGN: Cohort analytical study. SETTING: University medical center. PATIENTS: 488 patients with primary cutaneous melanoma who had no apparent metastatic disease. Patients were followed prospectively for at least 10 years. An independent validation sample of 142 patients was used to assess the stability of the model. MEASUREMENTS: Six clinical and pathologic variables that predict survival and are readily available to the clinician were used to develop a prediction model. The variables were tested for their association with death by using a univariate logistic regression model. Point estimates were generated for the probability of surviving melanoma at 10 years. Variables that were statistically significantly associated with survival were retained for testing in a logistic regression model. RESULTS: 488 patients were followed prospectively for a median of 13.5 years (minimum, 10.0 years; maximum, 20.5 years). The overall 10-year survival of the study group was 78%. Four variables were found to be independent predictors of survival. Presented as adjusted odds ratios, from strongest to weakest relative predictive strength, these variables were tumor thickness (odds ratio, 50.8), site of primary melanoma (odds ratio, 4.4), age of the patient (odds ratio, 3.0), and sex of the patient (odds ratio, 2.0). The four-variable model was significantly more accurate than tumor thickness alone, particularly for predicting death. Overall, use of the model reduced the error rate of the prediction of death by 50%. CONCLUSIONS: A prognostic model that uses four readily accessible variables more accurately predicts outcome in patients with primary melanoma than does tumor thickness alone. This four-variable model can identify patients at high risk for the recurrence of disease, an identification that becomes increasingly important as adjuvant therapies are developed for treatment of melanoma.

Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma.

BACKGROUND: Desmoplastic melanomas with and without neurotropism are thought to be more clinically aggressive than other melanomas of comparable thickness. This study evaluates the prognostic significance of desmoplasia and neurotropism in Patients with Stage I cutaneous melanoma completely excised at the initial presentation of disease and prospectively studied for a minimum of 8 years. METHODS: Desmoplasia and neurotropism were evaluated as single prognostic predictors in survival outcome of cutaneous Stage I melanomas and as variables in the University of Pennsylvania Pigmented Lesion Study Group 8-year survival model for Stage I melanoma. In addition, the clinical presentation and follow-up of melanomas with desmoplasia and/or neurotropism was compared with that of other types of cutaneous Stage I melanoma in patients also followed for a minimum of 8 years. RESULTS: Neurotropism was associated with a statistically significant decrease in survival in patients with melanomas with desmoplasia. A decrease in survival also was observed in other types of melanoma with neurotropism, but the difference was not statistically significant. Melanomas with neurotropism had a statistically significant increase in local recurrence. Desmoplasia was not associated with a statistically significant decrease in survival. CONCLUSION: Desmoplasia is not associated with a statistically significant decrease in the prognosis of patients with primary cutaneous Stage I melanoma. The more clinically aggressive behavior of desmoplastic melanomas observed in previous studies may be secondary to initial misdiagnosis and/or inadequate margin assessment of these lesions. Neurotropism, however, is associated with a statistically significant decrease in survival in patients with desmoplastic melanomas and is most likely associated with decreased reduces patient survival in other melanoma types. Neurotropism is also related to an increase in the frequency of local recurrence of melanoma.

Dysplastic nevi as a melanoma risk factor in patients with familial melanoma.

BACKGROUND: Familial melanoma has been associated with "clinically atypical moles" or "dysplastic nevi," (DN) which are markers for increased melanoma risk. In addition, melanomas in these kindreds present at a younger age, and tend to be multiple. METHODS: Melanoma incidence rates were determined for 710 members of 311 melanoma families, defined as kindreds in which melanoma had occurred in two or more blood relatives. Patients were classified either clinically or histologically as expressing DN. Melanomas that occurred before the first examination were recorded, and patients were followed prospectively for new melanomas. RESULTS: In prospective follow-up, the age-adjusted melanoma incidence rate was 1710/100,000 patient-years in family members with DN. In contrast, the rate was zero (no melanomas occurred) in family members without DN. For family members with DN, but without a history of melanoma, the age-adjusted incidence rate of melanoma was 413/100,000 patient-years, whereas the rate was 2779/100,000 patient-years in family members with DN and a history of melanoma. CONCLUSIONS: Dysplastic nevi and a history of melanoma are strong risk factors for subsequent melanoma. Prognostic factors are greatly improved for patients with melanomas diagnosed in follow-up compared with the first two melanomas in each kindred. These findings warrant surveillance of individuals with DN who are members of familial melanoma kindreds.

Natural history of dysplastic nevi.

BACKGROUND: Dysplastic nevi are markers of melanoma risk and potential precursors of melanoma. Few studies have addressed the natural history of dysplastic nevi. OBJECTIVE: Our purpose was to describe the changes observed in nevi over time in a cohort of our patients with dysplastic nevi. METHODS: We used a historical cohort design to study 153 patients with dysplastic nevi observed for a minimum of 5 years. Physical examination at completion of the study was compared with baseline overview and close-up photographs. Lesions excised during the study interval were assessed for history of change. RESULTS: Fifty one percent of all evaluated nevi (297 of 593) showed clinical signs of change during an average follow-up of 89 months. New nevi were common in adulthood and continued to form in more than 20% of patients older than 50 years of age. Nevi were observed to become more clinically atypical, less clinically atypical, and disappear in all age groups. In this small cohort rates of nevus change were not correlated with personal or family history of melanoma, sex, or total number of nevi. Total nevus counts and rates of nevus change were correlated with age. CONCLUSION: Dysplastic nevi remain clinically dynamic in adulthood. Our data suggest that the decrease in counts of dysplastic nevi associated with increasing age is only partly explained by the disappearance of nevi over time and probably reflects a tendency to larger numbers of nevi among more recent birth cohorts.

Lessons from tumor progression: the invasive radial growth phase of melanoma is common, incapable of metastasis, and indolent.

Primary melanoma generally evolves through three clinically and morphologically discernable tumor progression steps. Transformed melanocytes first proliferate above the epidermal basement membrane, then invade the papillary dermis (the in situ and invasive radial growth phases of melanoma), and subsequently develop the capacity to grow as a tumor (the vertical growth phase). Here, we address three aspects of the invasive radial growth phase that provide the rationale for viewing it as the critical lesion for melanoma detection and therapy. We determined the fraction of melanomas having this growth phase, tested its hypothesized incapacity to metastasize, and estimated its longevity. The high prevalence of this step in tumor progression was demonstrated in a data base of 624 patients, where at least 87% of melanomas exhibited a radial growth phase. The benignity of this lesion was evinced by the perfect metastasis-free survival of 161 patients treated for pure radial growth-phase melanomas and followed for a median of 13.7 years. Its indolence was evident in an analysis of the ages of 234 patients with superficial spreading melanomas without or with vertical growth phase: The cases with lesions having only radial growth phase were 4.3 years younger than those additionally having vertical growth phase (p < 0.05). These features of the invasive radial growth phase of primary melanoma, first described by Wallace H. Clark, make it a pivotal lesion in the evolutionary biology of melanocytic neoplasia and confirm its central place in public health programs to control melanoma mortality.

A cohort study of melanoma in patients with dysplastic nevi.

A historical cohort of 153 patients with dysplastic nevi was studied for the development of melanoma. Each subject had a minimum follow-up of 5 years, with an average study follow-up of 94 months. Eleven new melanomas developed in 11 patients between 11 and 143 months (average 61 months) into the study period. Age-adjusted melanoma incidence in the cohort was 692/100,000 person years. Development of melanoma was strongly correlated with prior personal and/or family history of melanoma. Even among the 89 patients with no personal or family history of melanoma, the age-adjusted incidence of melanoma was an alarming 154/100,000 person years. Within this small, non-randomly ascertained cohort no association could be discerned between melanoma incidence and total number of banal or dysplastic nevi. These findings support the public health significance of the recognition of dysplastic nevi and confirm the importance of family history in evaluating melanoma risk associated with dysplastic nevi.

Loco-regional nodal relapse in melanoma.

Two-hundred and seven patients without evidence of disease following lymph node dissection (LND) were stratified into three groups: Group A, lymph node relapse within the site of prior LND; Group B, lymph node relapse in a different, but regional, lymph node group; Group C, no lymph node relapse. Decreased survival was noted in both Groups A and B versus Group C. Prognostic factors were identified as: (i) axial or subungal/volar (subvolar) location and the number of positive lymph nodes at initial LND for nodal relapse within the same lymph node group; (ii) male gender, axial/subvolar location, and the number of histologically positive lymph nodes at initial LND for nodal relapse in a different, but regional lymph node group; (iii) relapse within the initial LND site for a decreased survival. Six of 10 patients with both axial/subvolar primaries and four or more positive lymph nodes developed a relapse within the dissection site post-LND. These prognostic factors describe a subset of patients who would be candidates for postoperative adjuvant local/regional and systemic therapy trials.

The prognostic implications of microscopic satellites in patients with clinical stage I melanoma.

Controversy exists as to whether microscopic satellites influence prognosis or patterns of progressive disease in patients with clinical stage I melanoma. Fifty patients with clinical stage I melanoma and microscopic satellites were prospectively studied from 1972 to 1984. To allow for complete histopathology assessment, 30 patients with microscopic satellites who were prospectively seen from 1972 to 1979 were matched to a cohort of 77 patients with vertical growth-phase melanoma without microscopic satellites according to six attributes. The matched cohort study showed that the presence of microscopic satellites appeared to be associated with increased local regional cutaneous and regional nodal disease and a significantly decreased actuarial disease-free survival. A Cox multivariate regression analysis that involved 384 patients with vertical growth-phase clinical stage I melanoma showed that the presence of microscopic satellites independently predicted a poorer disease-free survival and overall survival. Therefore, this study demonstrated that the presence of microscopic satellites correlated with a significantly decreased survival.

Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma. A case-control study.

The melanoma risk associated with dysplastic nevi outside the context of familial melanoma was studied by the case-control method. One hundred five newly diagnosed incident melanoma cases with negative family histories for familial melanoma and 181 controls (frequency matched for race, age, and sex) were studied by personal interview and cutaneous examination. The prevalence of dysplastic nevi was 41 (39%) of 105 in the cases and 13 (7%) of 181 in the controls. The odds ratio for dysplastic nevi by multiple logistic regression analysis simultaneously correcting for age, sex, eye color, hair color, actinic damage, freckles, and total number of nondysplastic nevi was 6.8 (95% confidence interval, 2.7, 16.9). This study supports the significance of dysplastic nevi as markers of increased risk for nonfamilial melanoma.

Model predicting survival in stage I melanoma based on tumor progression.

We used the lesional steps in tumor progression and multivariable logistic regression to develop a prognostic model for primary, clinical stage I cutaneous melanoma. This model is 89% accurate in predicting survival. Using histologic criteria, we assigned melanomas to tumor progression steps by ascertaining their particular growth phase. These phases were the in situ and invasive radial growth phase and the vertical growth phase (the focal formation of a dermal tumor nodule or dermal tumor plaque within the radial growth phase or such dermal growth without an evident radial growth phase). After a minimum follow-up of 100.6 months and a median follow-up of 150.2 months, 122 invasive radial-growth-phase tumors were found to be without metastases. Eight-year survival among the 264 patients whose tumors had entered the vertical growth phase was 71.2%. Survival prediction in these patients was enhanced by the use of a multivariable logistic regression model. Twenty-three attributes were tested for entry into this model. Six had independently predictive prognostic information: (a) mitotic rate per square millimeter, (b) tumor-infiltrating lymphocytes, (c) tumor thickness, (d) anatomic site of primary melanoma, (e) sex of the patient, and (f) histologic regression. When mitotic rate per square millimeter, tumor-infiltrating lymphocytes, primary site, sex, and histologic regression are added to a logistic regression model containing tumor thickness alone, they are independent predictors of 8-year survival (P less than .0005).

A comparison of local recurrence and resection margins for stage I primary cutaneous malignant melanomas.

A retrospective review of 552 patients with clinical stage I primary cutaneous malignant melanomas was undertaken comparing margins of resection and local recurrence between 1966 and 1981. The overall local recurrence rate was 8 per 552 (1.45 percent). We observed no instances of local recurrence in lesions less than 1.40 mm thick with resection margins of at least 1 cm. A comparison of resection margins greater than 2 cm versus less than 2 cm for lesions less than 1.00 mm thick showed no difference at the 0.05 level of significance for local recurrence (0 per 228 versus 2 per 154; 1.3 percent) or survival. While narrower margins of resection for thinner, low-risk stage I malignant melanomas appear safe, the exact minimum margin of resection needed to satisfy both oncologic and cosmetic considerations, whether 1 or 2 cm, will need to be determined by a large prospective, randomized study.