Acral lentiginous melanoma: a skin cancer with unfavourable prognostic features. A study of the German central malignant melanoma registry (CMMR) in 2050 patients.

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.

[Analysis of clinicopathological characteristics and prognostic factors of foot and ankle soft tissue and bone tumors].

Objective: To evaluate the clinicopathological characteristics of foot and ankle soft tissue and bone tumor, and to analyze the prognosis and the related factors of malignant tumors in this site. Methods: 74 patients with soft tissue and bone tumors of foot and ankle from January 2006 to February 2017 were retrospectively analyzed. The clinicopathological characteristics, the treatment and survival status of malignant tumors were followed up, and the clinical and therapeutic factors related to prognosis were analyzed. Results: Of the 74 patients, 34 were males and 40 were females. The male to female ratio was 1∶1.18; the age ranged from 12 to 64 years and the median age was 42 years. Tumors located in forefoot of 22 cases, 22 in midfoot, 10 in hind foot, 14 in ankle joint and 6 in multiple sites. 14 cases were bone tumors, including 7 benign and 7 malignant, and 60 cases were soft tissue tumors, including 14 benign and 46 malignant. The most common malignant soft tissue tumors were synovial sarcomas (13 cases), and the most common benign soft tissue tumors were hemangiomas (4 cases). 44 cases of malignant tumors underwent surgery were followed up, of which were 7 bone and 37 soft tissue malignant tumors. Limb salvage surgeries were performed in 33 cases and amputation in 11 cases. The median follow-up time was 69.8 months, and the median survival time was 40.7 months. The 1-year, 3-year and 5-year survival rate of soft tissue malignant tumors was 88.0%, 73.0%, and 63.0%, respectively. The 1-year, 3-year and 5-year survival rate of bone malignant tumors was 86.0%, 57.0% and 57.0%, respectively. Univariate analysis showed that the prognostic factors affecting 5-year survival rate were tumor size and adjuvant therapy (P<0.05). Patient's gender, age, tumor location, histological type and surgical procedure had no effect on overall survival(P>0.05). Multivariate analysis showed that tumor size was an independent prognostic factor (RR=7.262, P=0.005). Conclusions: Forefoot and midfoot are more common in foot and ankle soft tissue and bone tumors. Synovial sarcoma is the most common diagnosis in malignant soft tissue tumors, and hemangioma is the most common diagnosis in benign soft tissue tumors. The prognostic factor of malignant soft tissue and bone tumors in foot and ankle is tumor size. Patients with the tumor size of 5 cm or more have a worse prognosis.

Acral lentiginous melanoma: who benefits from sentinel lymph node biopsy?

BACKGROUND: There are significant clinicopathological, genetic, and biological differences between acral lentiginous melanoma (ALM) and other types of melanoma. OBJECTIVE: We sought to investigate the use of sentinel lymph node (SLN) biopsy for patients with ALM. METHODS: This was a retrospective review of 116 patients with primary ALM. Melanoma-specific and disease-free survival were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazards regression model. RESULTS: All patients were Japanese (48 male and 68 female). Metastases in SLN were noted in 13 of 84 patients who underwent SLN biopsy. No patients with thin ALM (≤1 mm) and only 2 patients with nonulcerated ALM had tumor-positive SLN. Patients with positive SLN had significantly shorter melanoma-specific survival (5-year survival rate, 37.5% vs 84.3%; P < .0001) and disease-free survival (5-year survival, 37.5% vs 77.9%; P = .0024). Among patients with thick (>1 mm) ALM, the influence of SLN positivity on melanoma-specific survival was increased (5-year survival, 22.7% vs 80.8%; P = .0005). LIMITATIONS: This was a retrospective study and had a small sample size. CONCLUSIONS: SLN biopsy should be considered for patients with thick or ulcerated ALM. For patients with thin or nonulcerated ones, it may be of limited importance.

Broiler flocks in production systems with slower-growing breeds and reduced stocking density receive fewer antibiotic treatments and have lower mortality.

In the Netherlands, the number of broiler production systems with higher welfare standards, using slower-growing broilers and decreased stocking densities, has increased over the last decade. This study aimed to investigate the effect of this change on antibiotic treatments, mortality, and footpad lesions. Data from national monitoring databases from 2013 to 2021 were used, resulting in 113,380 included flocks from 917 farms. Flocks were divided into conventional (CONV), medium-growing (MED), and slow-growing (SLOW), based on breed and slaughter age (median age: CONV 42 d; MED 50 d; SLOW 56 d). Generalized mixed-effect models were created to compare antibiotic treatments in and after the first week, total on-farm mortality, and footpad lesion scores between these 3 production systems. Year, quarter, flock size, thinning, number of houses, and regional density of poultry farms were included as fixed effects. Random effects were farm and veterinary practice in all models, with an additional random slaughterhouse effect to describe footpad lesions. Probability of treatment in the first week of age in CONV flocks overall years (7.2%, 95% CI [5.9, 8.7]) was higher than in MED (2.0%, 95% CI [1.6, 2.5]) and SLOW flocks (1.3%, 95% CI [1.0, 1.7]). Treatment probability after the first week was similarly higher in CONV flocks (14.7%, 95% CI [12.1, 17.6]) than in MED (3.2%, 95% CI [2.5, 4.0]) and SLOW flocks (2.2%, 95% CI [1.7, 2.9]). CONV flocks had a higher mean mortality (3.2%, 95% CI [3.0, 3.4]) than MED (2.0%, 95% CI [1.9, 2.1]) and SLOW flocks (1.9%, 95% CI [1.8, 2.0]). Regarding footpad lesions, CONV flocks had the highest mean scores (range 0-200) over all years, whereas SLOW flocks had the lowest scores (CONV: 46.1, 95% CI [42.1, 50.6]; MED: 21.3, 95% CI [18.9, 24.0]; SLOW: 13.2, 95% CI [11.5, 15.1]). This analysis of data from flocks over a 9-yr period indicates that switching from conventional to alternative production systems with higher welfare standards could positively affect broiler health and antibiotic use.

Melanoma of the hand and foot: epidemiological, prognostic and genetic features. A systematic review.

BACKGROUND: While early recognition and prognosis of melanoma as a whole have improved, particular forms of rarer, under-recognized or more severe tumours require increasing attention. Among them, melanomas located on the hand and/or foot (hand and foot melanoma, HFM) have been the subject of few and heterogeneous studies, with variable and sometimes confusing results, and have not been targeted to date by comprehensive literature reviews. OBJECTIVES: To perform a formal, systematic review of the literature, focusing on epidemiology, risk factors, prognosis and genetic characteristics of HFM. Methods All data sources were identified through searches on Medline, Scopus and Cochrane databases. Articles were selected and evaluated according to predefined quality criteria. RESULTS: Among 1185 articles screened for relevance, 37 met the inclusion criteria. Data analysis brought to light important particularities of HFMs: they are rare in all ethnic groups of developed countries, but have been insufficiently studied in the developing world. About half are of the specific acral lentiginous melanoma (ALM) subtype. Previous trauma and naevi on the soles/toes were identified as two main risk factors in case-control studies. Genetic or environmental factors other than sun exposure are likely to play a role but require further investigation. Compared with melanoma at other sites, their prognosis is poor mainly as a consequence of later diagnosis, but possibly also because of an intrinsic negative effect of the HFM/ALM subtype. Standard prognostic factors of melanoma have been insufficiently validated to date in HFM. Finally, their molecular genetic particularities could lead to specific targeted therapies in the near future. CONCLUSIONS: Overall, HFM could represent a particular subgroup of rare, potentially severe melanomas, requiring specific management from their prevention up to their treatment.

The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma.

BACKGROUND: Malignant soft tissue tumors of the foot are extremely rare and thus can be prematurely excised without appropriate preoperative evaluation. The present study compares adverse effects between unplanned and planned surgical excisions. METHODS: We retrospectively reviewed the clinical records, radiographs, pathology reports and pathological specimens of 14 consecutive patients with soft tissue sarcoma of the foot among 592 with sarcomas between 1973 and 2009. We then compared the incidence and clinical outcomes after unplanned (UT; n = 5) and planned (PT; n = 9) surgical excisions of foot sarcomas. RESULTS: The most frequent diagnosis was synovial sarcoma (n = 4; 28.6%). The overall 5-year survival rates of the PT and UT groups were 65.6% and 60.0%, respectively, and the event-free 5-year survival rates were 63.5% and 40.0%, respectively. Event-free and overall survival rates did not significantly differ between the two groups. However, tumors were significantly larger in the PT group than in the UT group (p < 0.05). CONCLUSIONS: Unplanned resection lead to a relatively worse prognosis and a likelihood of recurrence despite additional resections. We recommend that soft tumors of the foot should only be excised after appropriate preoperative evaluation regardless of the size of the tumor.

Prognostic indicators of poor outcome in horses with laminitis at a tertiary care hospital.

This retrospective study investigated the factors associated with a poor outcome (death by euthanasia or from other causes) in horses treated for laminitis at a tertiary care hospital. Cases (n = 247) were defined as patients with laminitis that were euthanized or that died of other causes during hospitalization. Controls (n = 344) were patients with laminitis that survived to be discharged from the hospital. In the final multivariate analysis, the factors significantly associated with an increased risk for death and their respective odds ratios (OR) were as follows: Thoroughbred (OR = 1.57); racehorse (OR = 1.76); treatment with flunixin meglumine (OR = 1.76); vascular pathology (OR = 2.12); distal displacement of the third phalanx (OR = 2.68); pneumonia (OR = 2.87); and lameness of Obel grade II (OR = 2.99), grade III (OR = 9.63), or grade IV (OR = 20.48). The use of glue-on shoes significantly reduced the risk for death (OR = 0.36).

Tumor growth rate as a prognostic factor of acral melanoma in a Korean population.

Rapid growth of cutaneous melanoma is associated with aggressive histopathologic features and poor prognosis. However, the impact of growth rate (GR) in acral melanoma (AM) remains largely unknown.We performed this study to identify the impact of GR on lymph node metastasis and survival in AM.We analyzed cases of invasive AM diagnosed at our institution between 1998 and 2017. We investigated the impact of GR on the prognosis of AM.A total of 126 cases of invasive AM were included. Log (GR) was significant associated with lymph node metastasis in the univariate logistic regression analysis (P = .005). The log-rank test revealed statistically significant differences in disease-free survival (DFS) and disease-specific survival (DSS) among the GR quartiles. In the Cox regression analysis, log (GR) was an independent predictor for DFS (P = .041), but not for DSS in multivariate analysis. In the subgroup analysis, log (GR) was an independent predictor for early-stage (≤2A) AM (DFS, P = .002; DSS, P = .004).The limitations of this study include the retrospective design of the study and possible recall bias.Our results suggest that GR is an important prognostic factor for DFS and DSS in AM patients and an independent predictor for early-stage AM.

Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis.

In a recent study we detected marked differences in the antigenic profile of acral lentiginous melanoma (ALM) and nodular melanoma lesions. Furthermore, we showed that the human high molecular weight melanoma-associated antigen (HMW-MAA) is expressed with a significantly higher frequency in metastatic than in primary ALM lesions. Because of the potential role of HMW-MAA in the metastatic process of melanoma cells, in the present investigation we tested whether HMW-MAA represents a useful prognostic marker in ALM. Primary ALM lesions removed from 32 patients were stained with anti-HMW-MAA monoclonal antibody (mAb) in an immunoperoxidase reaction. The results were correlated with the expression of other markers defined by mAb, with clinical parameters of the disease, and with histopathological characteristics of the lesions. Only 9 of the 32 primary ALM lesions tested were stained by anti-HMW-MAA mAb. Expression of HMW-MAA was the only variable associated with patients' survival and disease-free survival. Both were significantly shorter in patients with HMW-MAA expression in their primary lesions. These results suggest that HMW-MAA may represent a novel prognostic marker in ALM, since phenotyping of primary ALM lesions with anti-HMW-MAA mAb may provide information about the prognosis of the disease which cannot be obtained with known prognostic parameters.

Insulin-Like Growth Factor II mRNA-Binding Protein 3 Expression Correlates with Poor Prognosis in Acral Lentiginous Melanoma.

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed with ALM via immunohistochemistry. Univariate and multivariate analyses for survival were performed, according to clinical and histologic parameters, using the Cox proportional hazard model. Survival curves were graphed using the Kaplan-Meier method. IMP-3 was over-expressed in 70 out of 93 tumors (75.3%). IMP-3 expression correlated with thick and high-stage tumor and predicted poorer overall, melanoma-specific, recurrence-free and distant metastasis-free survivals (P = 0.002, 0.006, 0.008 and 0.012, respectively). Further analysis showed that patients with tumor thickness ≤ 4.0 mm and positive IMP-3 expression had a significantly worse melanoma-specific survival than those without IMP-3 expression (P = 0.048). IMP-3 (hazard ratio 3.67, 95% confidence intervals 1.35-9.97, P = 0.011) was confirmed to be an independent prognostic factor for melanoma-specific survival in multivariate survival analysis. Positive IMP-3 expression was an important prognostic factor for ALMs.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan in patients with locally advanced soft tissue sarcomas: treatment response and clinical outcome related to changes in proliferation and apoptosis.

Hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan (HILP-TM) with or without IFN-gamma is a promising local treatment in patients with locally advanced extremity soft tissue sarcomas (STSs), with response rates of up to 84%. The mechanisms of the treatment response are poorly understood. Here, we determined the HILP-TM-induced changes in mitotic activity, proliferation, and apoptosis in 37 STSs; the additional effect of IFN-gamma; and the association of HILP-TM with treatment response and clinical outcome. On archival material, obtained before and 6-8 weeks after HILP-TM with (n = 15) or without (n = 22) IFN-gamma, the number of mitoses was counted, and the proliferation fraction was determined by immunohistological staining for the proliferation associated Ki-67 antigen (MIB1). Apoptosis was visualized by enzymatic detection of DNA fragmentation (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Clinical and histological response, follow-up status, and survival were recorded. The number of mitoses dropped 57% and proliferation rate decreased with 40% after HILP-TM, whereas the amount of apoptosis after HILP-TM more than doubled as before HILP-TM. The addition of IFN-gamma to HILP-TM did not influence the changes in tumor parameters and did not affect treatment response. A better clinical response to HILP-TM was correlated with high mitotic activity and low amount of apoptosis in tumor samples before HILP-TM. Patients with highly proliferative STS before and after HILP-TM had a relatively poor prognosis. Furthermore, patients who developed distant metastases after HILP-TM had a relatively high number of dividing cells in the tumor remnants after treatment.

Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity.

PURPOSE: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. METHODS AND MATERIALS: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). RESULTS: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. CONCLUSIONS: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet.

Effects and dose--response relationships of skin cancer and blackfoot disease with arsenic.

In a limited area on the southwest coast of Taiwan, where artesian well water with a high concentration of arsenic has been used for more than 60 years, a high prevalence of chronic arsenicism has been observed in recent years. The total population of this "endemic" area is approximately 100,000. A general survey of 40,421 inhabitants and follow-up of 1,108 patients with blackfoot disease were made. Blackfoot disease, so-termed locally, is a peripheral vascular disorder resulting in gangrene of the extremities, especially the feet. The overall prevalence rates for skin cancer was 10.6 per 1000, and for blackfoot disease 8.9 per 1000. Generally speaking, the prevalence increased steadily with age in both diseases. The prevalence rates for skin cancer and blackfoot disease increased with the arsenic content of well water, i.e., the higher the arsenic content, the more patients with skin cancer and blackfoot disease. A dose-response relationship between blackfoot disease and the duration of water intake was also noted. Furthermore, the degree of permanent impairment of function in the patient was directly related to duration of intake of arsenical water and to duration of such intake at the time of onset. The most common cause of death in the patients with skin cancer and blackfoot disease was carcinoma of various sites. The 5-year survival rate after the onset of blackfoot disease was 76.3%; the 10-year survival rate was 63.3% and 15-year survival rate, 52.2%. The 50% survival point was 16 years after onset of the disease.

Clinical outcomes of localized melanoma of the foot: a case-control study.

The controversy over whether melanoma of the foot has a poorer prognosis than melanoma of the leg remains unresolved. This investigation used a case-control design to address this issue. This design consisted of a survival analysis of 119 cases with localized melanoma of the foot and 238 controls with localized melanoma of the leg that were matched on prognostic factors including tumor thickness, ulceration, surgical treatment, gender, year of diagnosis, and age. There was a statistically significant difference between the survival rates of cases and controls. The 5-year survival rate for cases was 74.3% compared to 85.2% for controls. At 10 years, the survival rate was 63.6% for cases and 77.2% for controls. Cases experienced a higher percentage of distant recurrences than controls. These results imply that patients with melanoma of the foot have a poorer survival than patients with melanoma of the leg after controlling for prognostic factors.

The effect of misdiagnosis and delay in diagnosis on clinical outcome in melanomas of the foot.

BACKGROUND: Melanoma of the foot is often discussed as an uncommon tumor which, when it occurs, presents in nonwhite races. STUDY DESIGN: The tumor registry of a 650 bed community teaching hospital and the Connecticut Tumor Registry were retrospectively reviewed for the nine-year period from July 1980 to July 1989. Patient age, race, sex, incidence of misdiagnosis, and delay until definitive therapy were recorded. Tumor location, size, staging, follow-up, recurrence, and disease-free survival rates were also recorded and correlated with initial disease, stage, and misdiagnosis or delay. RESULTS: Twenty-six cases were identified at Bridgeport Hospital, and 140 cases were identified in the Connecticut Tumor Registry. Significant delay in diagnosis occurred in 68 percent of the cases from the hospital and at least 16 percent of the cases in the state tumor registry. Regardless of stage, melanoma of the foot had a worse prognosis than melanoma of the thigh and lower leg. Delays in diagnosis had no demonstrable effect on clinical outcome. CONCLUSIONS: Melanoma of the foot is not as rare as commonly suspected, and constituted 3 percent of the 4,562 melanomas reported in the state tumor registry for the nine-year period. The majority were in fair-skinned individuals, and misdiagnosis was common. It is the inherent aggressiveness of the tumor rather than the delay in diagnosis that accounts for the poor clinical outcome.

Melanoma of the foot.

We performed a prospective study of the results of treatment of primary cutaneous melanoma of the foot in 282 patients to determine if there were any factors that could predict survival. These patients were part of a group of 1018 patients who had primary cutaneous melanoma affecting the lower extremity. We found that 184 (65 per cent) of the 282 patients had a tumor that extended into the reticular dermis or subcutaneous tissue (a Level-IV or V lesion according to the system of Clark et al.). Sixty-three patients (22 per cent) had evidence of local, regional, or distant metastatic disease at the time of presentation. Location of the melanoma on the plantar aspect of the foot was found to be an independent variable that was associated with a poorer rate of survival (56 per cent at five years and 46 per cent at ten years) compared with a dorsally located melanoma (80 per cent at five years and 67 per cent at ten years). Subungual lesions were associated with an extremely low rate of survival (17 per cent at ten years); however, because of the small number of subungual lesions that were followed, the difference in survival between the patients who had a plantar lesion and those who had a subungual lesion was not significant (p = 0.52). Variables, in order of decreasing importance, that had independent prognostic significance for survival of patients who had a melanoma of the foot were the clinical stage of the lesion at the time of presentation (p < 0.001) and the age of the patient (p < 0.03), as determined by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant melanoma of the foot and ankle.

The records of sixty patients who had a malignant melanoma of the foot or ankle were reviewed retrospectively to determine the clinical features, prognostic factors, and distinguishing characteristics. Fifty-seven patients were white and three were black. There were forty-two women and eighteen men (a female-to-male ratio of 2.3 to 1). The mean age at the time of presentation was fifty-seven years (range, twenty-two to eighty-three years). The most common site of involvement was the plantar aspect of the foot. The mean duration of follow-up was forty-five months (range, three to 144 months). Kaplan-Meier life-table analysis revealed an over-all five-year survival rate of 63 per cent and an over-all ten-year survival rate of 51 per cent. The mean duration of survival for the patients who had a plantar or subungual lesion was significantly shorter than that for the patients who had a lesion at another site on the dorsal aspect of the foot or on the ankle (forty-seven compared with seventy-two months) (p = 0.02). The mean depth of the lesion, according to the criteria of Breslow, was 3.03 millimeters, and the mean level, according to the classification of Clark et al., was IV. According to the classification of the American Joint Commission on Cancer, forty-three patients had stage-I or II (local) disease, thirteen had stage-III disease (nodal or in-transit disease, defined as cutaneous or subcutaneous metastases more than two centimeters from the primary tumor but not beyond the regional lymph nodes), and four had stage-IV disease (distant visceral metastases) at the time of presentation. Lesions at plantar and subungual sites were also associated with a higher prevalence of clinical misdiagnosis compared with lesions on the dorsal aspect of the foot or on the ankle (p = 0.02). The misdiagnoses included a benign nevus (one patient), a paronychia (one patient), a pyogenic granuloma (two patients), a plantar wart (three patients), a ganglion cyst (one patient), a blister (two patients), and a traumatic lesion (five patients).(ABSTRACT TRUNCATED AT 250 WORDS)