Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

The predictive value of the sentinel lymph node in malignant melanomas.

At the beginning of a lymphogenous metastasizing process in malignant melanomas, the first tumor cells are found in the so-called sentinel lymph node (SLN), defined as the first tumor-draining lymph node. Its removal and histopathological examination enable us to discover metastases of malignant melanomas long before their possibility of detection by any other method. Since the beginning of 1995, we have performed more than 350 gamma-probe-guided sentinel lymphonodectomies (gamma-SLNE), without any clinical evidence of metastases as determined by lymphoscintigraphy. Using gamma-SLNE, the detection and excision of the SLN succeeded in nearly all patients. The SLNs were fixed in formalin, completely cut into 1-mm thin slices and stained for routine H&E histology and with S-100 and HMB-45. In persons with melanomas thinner than 0.75 mm, we never found micrometastases. However, the SLNs were positive in melanomas from 0.76 to 1.50 mm in about 7% of patients, in melanomas from 1.51 to 4.00 mm in about 21% and in tumors thicker than 4 mm in about 44%. In primary melanomas with satellite or in-transit metastases, the SLNs contained metastases in 75% of patients. Normally, a radical lymph node dissection (RLND) follows, as it is considered to be the necessary consequence following detection of tumor cells. The lymph nodes of the RLNDs contained further metastases in about 30% of patients. The probability of the involvement of lymph nodes other than the SLN correlates with the extension of tumor cells in the SLN. During our 4-year-follow-up, we observed only a single lymph node recurrence in a patient with a negative SLN (false negative rate of about 0.4%). The development of systemic metastasis correlates not only with the Breslow tumor thickness, but also with the extent of the involvement of the melanoma metastasis in the SLN. Summarizing, it can be said that gamma-SLNE has revolutionized melanoma surgery. Based on our data, it is absolutely necessary in the staging of malignant melanoma. In our opinion, the existing classification systems for staging lymph node involvement have to be revised in light of the results of SLNE.

Particles from mouse melanoma B16 containing reverse transcriptase and 70S RNA related to human melanoma cytoplasmic RNA.

The mouse melanoma B16 contains particles encapsulating high molecular weight RNA of 60--70S size associated with a reverse transcriptase. The [3H]DNA synthesized by these particles possesses homology with RNA isolated from a hamster melanoma and from three human malignant melanomas.

[Acryronitril as a contact allergen]. / Akrylnitril als Kontaktallergen

A case of allergic contact dermatitis following the use of a Plexidur finger splint is reported. The allergen was acrylonitrile, one of the original constituents of the polymer Plexidur.

[Diagnosis of herpes simplex diseases]. / Diagnostik von Herpes simplex-Erkrankungen

The diagnosis of herpes simplex diseases will be made on ground of the typical clinical symptoms in more than 90% of all cases. A very easy additional procedure is the Tzanck test. If possible, immunofluorescent microscopy and electron microscopy of negatively stained virus particles may be helpful. Remaining questions should be solved by further virological examination in special laboratories. Information about sampling and shipment of the diagnostic material (vesicle fluid, swabs from mouth and genital ulcers, blood etc.) should be obtained prior to collection.

[Circumscribed pseudolymphomas: definition, diagnosis and differential diagnosis]. / Umschriebene Pseudolymphome: Definition, Diagnose und Differentialdiagnose.

Pseudolymphomas are benign reactive inflammatory lymphoreticular proliferations in the skin with potency of spontaneously regression. Despite of different etiology the patho- and morphogenesis may be largely uniform. The differential diagnosis includes numerous chronic granulomatous processes, but above all true (malignant) lymphomas. Histologically there are characteristic the kind and pattern of the infiltrate as well as (mostly) the absence of typical signs of malignant proliferations.

[Lung edema and erosive gastroduodenitis as a sequela of inappropriate use of an adrenaline dose aerosol after wasp sting]. / Lungenödem und erosive Gastroduodenitis als Folge unsachgemässer Anwendung eines Adrenalin-Dosisaerosols nach Wespenstich.

Epinephrine (adrenaline) is an important drug in the treatment of severe anaphylactic reactions. Along with other drugs such as H1-antihistamines and glucocorticosteroids, it is found in every first aid kit for at-risk individuals, such as those who are allergic to insect stings. Subcutaneous or intramuscular injections if carried out by an untrained individual or the patient himself might give rise to potential problems. Therefore, it is common to prescribe epinephrine pressure aerosol as a safer alternative. If epinephrine aerosol is overused, it can cause serious problems. A patient developed by self-medication following a wasp sting lung edema as well as an erosive gastroduodenitis. She consumed two aerosol vials each of which contained about 73 mg of adrenaline. In order to avoid such incidents it is crucial that every doctor provides his or her patient with sufficient oral and written information regarding the correct use fo epinephrine inhalers.

[Finger tip necroses after dihydroergotamine medication in limited systemic scleroderma]. / Fingerkuppennekrosen nach Dihydroergotaminmedikation bei limitierter systemischer Sklerodermie.

A 78 year old women developed acute fingertip necrosis just a few days after starting dihydroergotamine. The lesions healed in 3 weeks after the medication was stopped. The patient had suffered from Raynaud syndrome for 5 years and limited systemic sclerosis was diagnosed during the necrotic episode. Advanced age and microangiopathies are contraindications to the use of ergot-containing preparations.

[Allergic contact dermatitis due to tromantadin (author's transl)]. / Allergische Kontakt-dermatitis durch tromantadin.

37 observations on allergic contact dermatitis due to tromantadine are reported. With the increasing distribution and application of this adamantane derivative, the incidence of this type of clinical picture will probably increase further. The attendant physician should therefore accordingly explain to his patients and inform them of the initial symptoms - presumably striking intensification and local extension of the herpes eruption in spite of intensive treatment.

[Dacarbazine (DTIC) therapy and the Budd-Chiari syndrome]. / Dacarbazin (DTIC)-Therapie und Budd-Chiari-Syndrom.

A case of a 58 years old female is presented, who died because of a Budd-Chiari-syndrome. This complication had developed during treatment with Dacarbazine (DTIC), which was given after surgical removal of a malignant melanoma. The causative relation between the Budd-Chiari-syndrome and this cytostatic drug is discussed, even though the influence of other drugs cannot be excluded.

Loosening of a total hip prosthesis at contact allergy due to benzoyl peroxide.

It is reported that a 62-year-old man with total hip prosthesis developed a recurrent sterile fistula and loosening of his prosthesis due to allergy to the bone cement component benzoyl peroxide.

[Cyclosporin A in the treatment of pemphigus foliaceus and pemphigus erythematosus]. / Cyclosporin A in der Behandlung von Pemphigus foliaceus und Pemphigus erythematosus.

We present the cases of two female patients with pemphigus foliaceus and pemphigus erythematosus, respectively, who did not respond to long-term azathioprine and prednisone treatment in high dosages. In both patients the skin condition improved nearly completely after therapy with cyclosporine A (3.5-6.5 mg/kg per day) in combination with prednisone (7.5-10 mg every 2 days). We did not observe any side-effects during 1 year of this therapy.

[Malignant melanoma in lupus (tuberculosis cutis luposa)]. / Malignes Melanom in lupo (Tuberculosis cutis luposa).

We report on a 72 years old man showing a strikingly fast spreading malignant melanoma developing on a lupus vulgaris which had existed since childhood. The coincidence of both diseases is obviously extremely rare. A pathogenetic relationship between melanoma and lupus vulgaris, such as claimed for carcinoma in lupo, especially after X-ray irradiation, is not inferable.

[Steroid receptors in malignant melanomas]. / Steroidrezeptoren bei malignen Melanomen.

Epidemiological and experimental investigations have led to the hypothesis that the growth of malignant melanoma is induced by hormones. The demonstration of free-hormone binding sites in melanoma tissue may help to determine the validity of this hypothesis, as receptors are necessary for the transformation of hormonal action. The DCC assay with subsequent saturation analysis was used for the demonstration of specific cytoplasmatic binding sites of steroid hormones. The presence of free-cytosolic estrogen-, progesterone- and glucocorticosteroid receptors was investigated in 50 melanoma samples from 46 patients. In 20 of the 50 specimens, free estrogen and progesterone receptors were found. Free-glucocorticosteroid receptors we found in 10 cases. The use of four fold-labeled estradiol (2,4,6,7-[3]-17 beta-estradiol) in the DCC assay produced a false-positive demonstration of free-estrogen receptors. Tyrosinase hydroxylates estradiol at the C2 level of the steroid. Using fourfold labeled estradiol, tritium is separated at the C2 position, thus forming radioactive water in the cytosol which mimics high, free-estrogen binding sites. The use of twofold-labeled estradiol or L-dopa in the experiments with fourfold labeled estradiol produced no false-positive determinations of estrogen receptors. The demonstration of receptors in malignant melanomas was unaffected by the sex of the patient. Also, the type of malignant melanoma, the invasion level, and the prognostic index did not show a correlation with the presence of the various hormone receptors. In metastases, free steroid hormone receptors were detected less often than in the primary tumor.

The Augsburg experience: histological aspects and patient outcomes.

In Augsburg, sentinel lymphonodectomy (SLNE) was introduced into melanoma treatment in 1994. Diagnostic accuracy has been improved by early identification of sentinel lymph node (SLN) micrometastases and even more by their histomorphometric assessment. The S classification defines three categories of SLN metastases, S1 to S3, supplemented by S0 in the absence of metastasis. It is the leading predictor for the status of the remaining regional lymph nodes and an independent prognosticator for distant metastasis and survival. This should find consideration in adjuvant therapy trials. The pivotal question of whether SLN-guided surgery itself achieves survival benefit has been approached by a follow-up study that compared 387 SLNE-treated patients with 473 patients from the pre-SLNE era. In contrast to nonsignificant differences in patients with thin and very thick primary tumors, death from intermediate-thickness melanoma (1.51 to 4 mm) occurred significantly more often in the watch-and-wait group versus the SLNE group. These results must be validated by prospective randomized trials (e.g., NCI 29605).

["Sentinel" lymphonodectomy with scintillation detector. A new strategy in treatment of malignant melanoma]. / Die "sentinel" Lymphonodektomie mittels Szintillationsdetektor. Eine neue Strategie in der Behandlung maligner Melanome.

For decades the results of elective lymph node dissection (ELND) are differently discussed, so that it is not definitely recommended at present the less so since the morbidity of this operation can't be neglected. Since the beginning of 1995 we practice a gamma-probe guided sentinel lymphonodectomy (SLNE) on patients with melanoma from a Breslow tumor thickness of 1 mm upward, after injecting a colloidal 99m-Tc labelled tin (II) - sulfide solution around the tumor or the scar, if the tumor has been excided before. By this method, that allows a selection of patients who according clinically to a stage I or II (UICC) but even histopathologically to a stage III and who are profiting of a removal of the regional lymph nodes, the sentinel node can be exactly localised, tissue-sparing removed at minimal complication rates and the completeness of the removal can be verified by measurements of the radioactivity. When finding metastases in the histopathological examination of the node a dissection of the whole region follows.

Primary therapy of malignant melanomas: sentinel lymphadenectomy.

BACKGROUND: Each melanoma is drained by one or, occasionally, several individual lymph nodes within the nearest lymph node region (sentinel lymph node). OBJECTIVE: By histopathologic examination of the removed sentinel lymph node (SLN), it is possible to select patients clinically according to stage I or II (UICC classification), but who, microscopically, represent stage III. METHODS: Sentinel lymphadenectomies (SLNEs) were performed initially by the vital blue dye technique, and later by gamma-probe guidance only. The removed SLNs were examined by hematoxylin and eosin as well as immunohistochemical stains (S100, and HMB 45). RESULTS: We have performed 115 gamma-probe-guided SLNEs in 100 patients. The SLN could be found in all cases. In pT3 + 4 melanomas, 27.5% of the SLNs were positive; in only one patient with a pT2 tumor were micrometastases found. CONCLUSIONS: gamma-Probe-guided SLNE is a reliable procedure with minimal complications that should be performed in all pT3 + 4 (intraoperative frozen section histology) melanomas without clinically evident metastases.