The impact of nodal tumour burden on lymphoscintigraphic imaging in patients with melanomas.

PURPOSE: To retrospectively study the influence of nodal tumour burden on lymphoscintigraphic imaging in 509 consecutive patients with melanomas. METHODS: Bidirectional lymphatic drainage, the clear depiction of an afferent lymphatic vessel, time to depiction of the first sentinel lymph node (SLN) and number of depicted and excised nodes were recorded. Nodal tumour load was classified as SLN-negative, SLN micrometastases or macrometastases. RESULTS: In the overall population, using multivariate regression analysis, a short SLN depiction time was significantly associated with the depiction of a greater number of radioactive nodes, a short distance between the primary tumour site and the nodal basin, younger age and lower nodal tumour burden. The proportion of patients with clear depiction of an afferent lymphatic vessel depended on the nodal tumour load (46% in SLN-negative patients, 57% in SLN positive patients, and 69% in patients with macrometastases; P = 0.009). Macrometastasis was significantly associated with delayed depiction of the first radioactive node and a greater number of depicted hotspots. In patients with clinically nonsuspicious nodes, i.e. the classical target group for SLN biopsy, clear depiction of an afferent vessel was significantly associated with a higher number of SLNs during dynamic acquisition, SLN micrometastasis and a higher overall number of metastatic lymph nodes after SLN biopsy plus completion lymphadenectomy. The excision of more than two SLNs did not increase the metastasis detection rate. In patients with bidirectional or tridirectional lymphatic drainage, the SLN positivity rates for the first, second and third basin were 25.4%, 11.7% and 0.0 %, respectively (P = 0.002). CONCLUSION: In patients with clinically nonsuspicious lymph nodes, clear depiction of an afferent lymph vessel may be a sign of micrometastasis. Macrometastasis is associated with prominent afferent vessels, delayed depiction of the first radioactive node and a higher number of depicted hotspots.

Assessment of melanoma histotypes and associated patient related factors: basis for a predictive statistical model.

BACKGROUND: Certain melanoma histotypes carry a worse prognosis than others. We aimed to identify patient related factors associated with specific melanoma histotypes. PATIENTS AND METHODS: Single center study including 347 melanoma patients, prospectively assessed for 22 variables leading to a database of more than 7,600 features. RESULTS: Melanomas were histologically categorized as superficial spreading (SSM, 70.6%), nodular (NM; 12.7%), acrolentiginous (ALM; 4.0%), lentigo maligna (LMM; 3.8%), or unclassified melanoma (UCM; 8.9%). Well recognized melanoma risk indicators (i. e. many atypical nevi, freckles, previous melanoma), were significantly associated with SSM and LMM histotypes. NM and ALM patients carried significantly less common and/or atypical nevi. NM were mostly self-detected or detected by relatives. In contrast, SSM, LMM, and ALM were most frequently detected by dermatologists. NM and UCM were preferentially located on poorly observable sites, SSM on the lower limbs, ALM on plantar sites, and LMM on the head and neck. ALM and LMM patients were significantly older than other patients. A multinomial logistic model was designed to predict a certain melanoma histotype (overall accuracy 81%), which could be helpful to focus the attention of clinicians or may be integrated into fully automated diagnostic algorithms. CONCLUSIONS: Melanoma histotypes show significant differences regarding patients' characteristics.

Sentinel node biopsy improves prognostic stratification in patients with thin (pT1) melanomas and an additional risk factor.

BACKGROUND: Sentinel lymph node (SLN) biopsy (SLNB) for pT1 melanomas is not generally recognized as a clinical standard. We studied the value of SLNB for pT1 melanoma patients having at least one additional risk factor. PATIENTS: Among 931 patients with SLNB, 210 had pT1 melanomas. All of the latter showed at least one of the following risk factors: ulceration (4 %) Clark level IV (44 %), nodular growth pattern (11 %), mitoses (59 %), regression (38 %) or age ≤ 40 years (27 %). RESULTS: In this selected pT1 population, we observed a surprisingly high SLN positivity rate of 18 %. The melanoma-specific overall survival significantly depended on SLN status. Compared with Clark IV, a lower invasion level (Clark II/III) was associated with a higher proportion of positive SLNs (25 vs. 10 %; p < 0.01). There was a trend towards a higher SLN positivity rate in younger patients (p = 0.06). Breslow, ulceration, mitoses, nodular growth pattern, and sex did not reach significance. Regression was significantly more frequently found in very thin melanomas (≤ 0.75 mm) and tended to be significant in this subgroup (p = 0.075). CONCLUSIONS: SLNB improves prognostic stratification in patients with thin melanomas having an additional risk factor. Clark level IV most likely does not belong to these risk factors. The impact of regression deserves further consideration. Our data suggest that SLNB should be offered to patients with thin melanomas, if ulceration, nodular growth pattern, mitoses, or regression are present, or if the patient is younger than 40 years of age.

Individualized surgery: gamma-probe-guided lymphadenectomy in patients with clinically enlarged lymph node metastases from melanomas.

BACKGROUND: The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins. PATIENTS AND METHODS: Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive. RESULTS: A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases. CONCLUSION: In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed.

Age as a key factor influencing metastasizing patterns and disease-specific survival after sentinel lymph node biopsy for cutaneous melanoma.

In our study, we investigated the impact of the constitutional factor age on the clinical courses of melanoma patients with sentinel lymph node (SLN) biopsy. Descriptive statistics, Kaplan-Meier estimates, logistic regression analysis and the Cox proportional hazards model were used to study a population of 2,268 consecutive patients from three German melanoma centers. Younger age was significantly related to less advanced primary tumors. Nevertheless, patients younger than 40 years of age had a twofold risk of being SLN-positive (p < 0.000001). Of the young patients with primary melanomas with a thickness of 0.76 mm to 1.0 mm, 19.7% were SLN-positive. Using multivariate analysis, younger age, increasing Breslow thickness, ulceration and male sex were significantly related to a higher probability of SLN-metastasis. During follow-up, older patients displayed a significantly increased risk of in-transit recurrences (p = 0.000002) and lymph node recurrences (p = 0.0004). With respect to melanoma specific overall survival the patient's age was highly significant in the multivariate analysis. The unfavorable effect of being older was significant in the subgroups with positive and negative SLNs. Age remained also significant for the survival after the onset of distant metastases (p = 0.002). In conclusion, the patient's age is a strong and independent predictor of melanoma-specific survival in patients with localized melanomas, in patients with positive SLNs and after the onset of distant metastases. Younger patients have a better prognosis despite their higher probability of SLN metastasis. Older patients are less frequently SLN-positive but have a higher risk of loco-regional recurrence.

The popliteal fossa - a problem zone for sentinel lymphonodectomy.

BACKGROUND: The impact of lymphatic drainage to popliteal sentinel lymph nodes (SLNs) has yet to be explored in detail. PATIENTS AND METHODS: We performed lymphoscintigraphy on 663 patients with cutaneous melanomas. The following day sentinel lymphonodectomy was performed. SLNs were studied on serial sections with both histology and immunohistochemistry. RESULTS: 166 patients had a melanoma located on the foot, the lower leg or the knee, i. e., the potential of lymphatic drainage to the popliteal lymph nodes. On lymphoscintigraphy, only 16 patients (9.6 %) showed popliteal SLNs. A popliteal SLN was surgically identified in only 6 of the 16 patients. The reason for the poor identification rate was exhausted radioactivity in the small popliteal nodes the day after lymphoscintigraphy. In 3 cases, popliteal SLN metastasis was diagnosed. All but one patient had an additional drainage to the inguinal lymph nodes; inguinal SLN metastasis was diagnosed in 7 patients. Even all 16 patients showed lymphatic drainage to iliac lymph nodes, metastasis in the pelvis was diagnosed in 4 patients. CONCLUSIONS: Popliteal SLNs are observed in less than 10 % of the patients with melanomas of the distal leg. In the case of suspected popliteal drainage, lymphoscintigraphy should be performed on the day of sentinel lymphonodectomy because the radioactivity of the small and deeply situated popliteal nodes diminishes rapidly. With respect to complete lymphadenectomy, decision-making is difficult since three nodal basins (popliteal, inguinal and iliac) may harbor metastases.

Solitary cutaneous nodule of blastic plasmacytoid dendritic cell neoplasm progressing to overt leukemia cutis after chemotherapy: immunohistology and FISH analysis confirmed the diagnosis.

Blastic plasmacytoid dendritic cell (BPDC) neoplasm, formerly called blastic natural killer cell lymphoma or CD4+/CD56+ hematodermic neoplasm, is a rare tumor entity, now regarded to be derived from the plasmacytoid dendritic cell (PDC) lineage. Because over 90% of patients present with skin lesions usually early in their disease, dermatologists have to be familiar with the specific diagnostic features and the clinical course of this devastating disease. We present a woman with a long standing solitary skin tumor of BPDC neoplasm, who experienced a deleterious clinical course, which is typical for this disease. Phenotypic and karyotypic characteristics distinguishing this tumor from myelomonocytic leukemia with skin involvement are presented.

Postoperative morbidity of lymph node excision for cutaneous melanoma-sentinel lymphonodectomy versus complete regional lymph node dissection.

For patients with melanoma metastasis to a sentinel lymph node, subsequent complete regional lymph node dissection (CLND) is currently regarded to be the surgical standard. This approach, however, has not been confirmed by controlled studies, so that surgical morbidity is of primary importance. Using clinical examination and a questionnaire, we determined morbidity in 315 patients with axillary or inguinal lymph node excision on whom 275 sentinel lymphonodectomies (SLNEs) and 90 CLNDs were performed. The overall incidence of at least one complication following SLNE was 13.8%. The short-term complication rate was 11.3% (allergic reaction to blue dye 0%, wound breakdown 0%, haematoma 2.5%, wound infection 3.6%, seroma 6.9%). The incidence of long-term complications was 4.1% (persistent tattoo 0.4%, functional deficit 0.4%, nerve dysfunction/pain 0.7% or swelling 2.5%). All complications were mild. Significantly, the complication rate was not higher for patients aged 70 years or older. After CLND, the overall complication rate was significantly higher (65.5%, P<0.000001). The incidence of short-term complications was 50% (haematoma 0%, wound breakdown 6.7%, wound infection 24.7% or seroma 34.8%). The incidence of long-term complications was also 50% (nerve dysfunction/pain 8.9%, functional deficit 16.8%, swelling 37.1%). Overall, inguinal lymph node excision was burdened by a higher complication rate (P=0.015). Age and sex did not influence postoperative morbidity. No deaths linked to either procedure were noted. Complication rates after SLNE are low and most complications are minor and short-lasting. In contrast, CLND has been demonstrated to be a major and potentially morbid surgical procedure. This highlights the importance of testing the therapeutic value that CLND adds to the sentinel lymph node procedure.

Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases.

Infliximab is a monoclonal antibody directed against TNF-alpha. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role.

Sentinel lymph node status is the most important prognostic factor for thick (> or = 4 mm) melanomas.

BACKGROUND: The value of the status of the sentinel lymph node (SLN) in patients with thick melanomas (Breslow thickness > or = 4 mm) is controversial. PATIENTS AND METHODS: Using Kaplan-Meier estimates and Cox regression models, we studied 152 patients with primary melanomas > or = 4 mm thickness who underwent sentinel lymph node excision (SLNE) at the university hospitals of Hannover and Göttingen, Germany, between 1998 and 2006. RESULTS: The median tumor thickness was 5.2 (4-18) mm; 58.5% of primary melanomas were ulcerated. Micrometastasis to a SLN was found in 48.7%. The patients with positive SLNs were significantly younger than those with negative SLN (p = 0.01). Of the complete lymph node dissections, 32% contained positive non-SLN. The estimated 5 year recurrence-free survival was 42.5 +/- 5% (+/- standard error) (26.3 +/- 6.6% after positive SLNE, 58.7 +/- 7.1% after negative SLNE). The 5 year overall survival rate was 53.2 +/- 5.4% (37.5 +/- 8.1% after positive SLNE, 67.6 +/- 6.7% after negative SLNE). By multivariate analysis, the SLN was a highly significant predictor for overall survival (p = 0.007, relative risk 2.3, 95%, confidence interval 1.2-4.2). The overall survival was significantly associated with penetration of nodal metastases into the SLN > 0.3 mm (p = 0.001). Other parameters such as tumor thickness, ulceration, age and sex were not significant. In the subgroup of patients with negative SLN, neither tumor thickness nor ulceration was significant. CONCLUSIONS: The status of the SLN represents the most important prognostic parameter in patients with thick melanomas, whereas other parameters such as tumor thickness and ulceration loose their prognostic value.

Association of Patient Risk Factors and Frequency of Nevus-Associated Cutaneous Melanomas.

IMPORTANCE: The reported frequencies of associations between primary cutaneous melanomas and melanocytic nevi vary widely between 4% and 72%. However, earlier histopathologic studies were limited by their retrospective design and did not assess the influence of important patient-related risk factors. OBJECTIVES: To identify the frequency of nevus-associated melanomas and correlate patient- and melanoma-related factors. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, observational study with systematic documentation of melanoma risk factors, clinical and dermoscopic criteria of excised lesions, and results of histopathologic examination was conducted at a university-based dermatology clinic. Participants included 832 patients at high risk for developing melanoma. Evaluation was performed at regular intervals between April 1, 1997, and May 31, 2012, and data analysis was conducted between September 1, 2012, and December 31, 2013. MAIN OUTCOMES AND MEASURES: Assessment of the frequency of nevus-associated melanoma and the influence of patient- and melanoma-related factors on their manifestation. RESULTS: During the study, 190 melanomas (81 [42.6%] in situ and 109 [57.4%] invasive) were diagnosed in 113 of the 832 patients (13.6%); there were 42 women (37.2%) and 71 men (62.8%). The median (SD) Breslow thickness of invasive melanomas was 0.42 (0.43) mm. Histopathologic examination revealed remnants of melanocytic nevi in 103 melanomas (54.2%). Most nevus-associated melanomas were found on the trunk (67 [65.1%]); however, statistical significance for the localization was not present (P = .06). In univariate analyses, reported as odds ratios (95% CIs), nevus-associated melanomas were found significantly more frequently in patients of lower melanoma risk (risk group 1 [>50 common and/or ≤ 3 atypical nevi], 2.75 [1.14-6.64]; P = .02), with more than 100 nevi (1.63 [1.02-3.60]; P = .04), or with the diagnosis of in situ melanoma (14.01 [6.14-31.96]; P < .001). In contrast, nevus-associated melanomas were found significantly less frequently in patients with 1 or more previous melanomas (0.28 [0.21-0.83]; P = .005). All other factors (eg, age, skin type, hair color, and melanoma thickness) showed no significant influence on the manifestation of nevus-associated melanomas. These observations were confirmed in a separate analysis including all 109 invasive melanomas. Multivariate regression analysis identified 3 independent patient-related factors (high nevus count, low risk for melanoma, and female sex) and 1 melanoma-related factor (in situ melanoma) to be indicative of a significantly increased probability of nevus-associated melanomas. CONCLUSIONS AND RELEVANCE: In this prospective study of a high-risk patient cohort, 54.2% of primary melanomas were associated with melanocytic nevi. Patients with many nevi and without previous melanomas or traits of familial atypical mole and multiple melanoma syndrome had a higher frequency of nevus-associated melanomas. These patients could thus benefit from sequential digital dermoscopy in addition to total-body photography.

Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma: A Retrospective Multicenter Study in 2653 Patients.

UNLABELLED: The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. PATIENTS AND METHODS: Kaplan-Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively.The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false-negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases.The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan-Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken.