Bettina Schlagenhauff

Metastatic pathways and time courses in the orderly progression of cutaneous melanoma

Summary Background  It is known that two‐thirds of patients who develop clinical metastases following treatment of a primary cutaneous melanoma initially present with locoregional metastases and one‐third initially present with distant metastases. However, few reports in the literature give detailed figures on different metastatic pathways in cutaneous melanoma.

Prospective Evaluation of a Follow-Up Schedule in Cutaneous Melanoma Patients: Recommendations for an Effective Follow-Up Strategy

PURPOSE To prospectively examine and evaluate the results of follow-up procedures in a large cohort of cutaneous melanoma patients. PATIENTS AND METHODS This was a prospective study in 2,008 consecutive patients with stage I to IV cutaneous melanoma from 1996 to 1998 on the yield of stage-appropriate follow-up examinations according to the German guidelines. Documentation of patient and follow-up data comprised patient demography, primary tumor specifics, and any clinical and technical examinations performed. The detection of metastasis was classified as early or late, and the means of their detection and the resulting overall survival probabilities were examined. RESULTS A total of 3,800 clinical examinations and 12,398 imaging techniques were documented. Sixty-two second primary melanomas in 46 patients and 233 disease recurrences in 112 patients were detected during this time. In stage I to III disease, physical examination was responsible for the discovery of 50% of all recurrences. In the primary tumor stages, 21% of all recurrences were discovered by lymph node sonography, with the majority being classified as early detection. Forty-eight percent of the recurrences were classified as early detection, and these patients had a significant benefit of overall survival probability. CONCLUSION The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.

Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma

In regional lymph node metastasis of cutaneous melanoma, the number and volume of involved lymph nodes are the most important prognostic factors. Several studies have revealed that palpation of the lymphatic drainage area(s) and regional lymph nodes has a high rate of false‐negative results during follow‐up. The aim of the current study was to assess the sensitivity and specificity of ultrasound versus clinical diagnosis in the detection of subcutaneous and regional metastases.

Patterns of local horizontal spread of melanomas: consequences for surgery and histopathologic investigation.

Understanding local spreading patterns of melanomas is a precondition for the localized surgical treatment and histopathologic investigation. We used hematoxylin and eosin-stained paraffin sections for a two-phase, cellular and microscopic study of patterns of lateral spread in superficial spreading melanomas (SSMs), nodular melanomas (NMs), lentigo maligna melanomas (LMMs), and acral lentiginous melanomas (ALMs). Complete histologic examination of vertical excisional margins was carried out with paraffin sections 5 mm beyond the clinical tumor border of 1395 SSMs, 376 NMs, 179 LMMs, 46 ALMs, and 37 acrally located SSMs or NMs. Further sections of embedded material were analyzed when tumor-positive margins were found. In case of continuous tumor spread, reoperations were continued until the tissue was free of tumor cells. In case of noncontinuity, a final excision was made to a minimum safety margin of 10 to 20 mm. Concentrically consecutive, 5-microm thick hematoxylin and eosin-stained sections were taken from the outside of a 10-mm safety margin inward to the clinical borders of 34 SSMs, five NMs, 10 LMMs, and five ALMs. Noncontinuous subclinical spread was found in all SSMs and NMs in the form of few isolated cell nests at the epidermis-dermis junction. Ninety-two percent of these were located within 6 mm of the central tumor. All LMMs and ALMs showed a clearly demonstrable, uninterrupted spread into the periphery at the epidermis-dermis junction, too, usually in groups of outgrowths. The probability of finding these outgrowths 5 mm beyond the clinical tumor border was 54% in LMM and ALM. Complete histologic examination of vertical excisional margins (micrographic surgery) is therefore the therapy of choice only for LMM and ALM and is inefficient for SSM and NM.

Awareness and early detection of cutaneous melanoma: an analysis of factors related to delay in treatment

Factors associated with the detection of cutaneous melanomas and reasons for delay in diagnosis were investigated in 429 patients with histologically proven melanoma operated on between January 1993 and June 1996. Patients were interviewed using a standardized questionnaire. In 25% of patients, treatment was delayed for more than 1 year from the time they first noticed a suspicious pigmented lesion. Melanoma was detected by the patients themselves in 67% of women and 45% of men. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion. The role of sun exposure and of naevi as risk factors for melanoma, as well as the potential benefit of early treatment, were known by 87%, 66% and 82% of the patients, respectively. However, melanoma awareness had no impact on the time period between first observation of skin changes and treatment. Among the factors associated with delay in melanoma diagnosis, an initial incorrect diagnosis as a benign lesion by the physician first visited (in 18% of all cases) had the highest significance. Patients detecting their lesions themselves were treated significantly later than patients in whom others had remarked on changes in a naevus. Furthermore, melanomas of the head and neck were treated later than melanomas at other body sites. Further efforts to educate both the public and the medical profession are essential to ensure earlier treatment for cutaneous melanomas.

Aminopeptidase M and dipeptidyl peptidase IV activity in epithelial skin tumors: a histochemical study

The activities of microsomal alanylaminopeptidase (APM EC 3.4.11.2) and of dipeptidyl dipeptidase IV (DPP IV EC 3.4.14.5) were histochemically studied in frozen sections of normal skin, seborrheic keratosis, basal cell carcinoma, solar keratosis, Bowens disease and squamous cell carcinoma using amino acid‐ or peptide‐4‐methoxy‐2‐naphthylamides as specific chromogenic substrates. Compared to biochemical and immunohistochemical methods, the histochemical technique used in this study allows distinct localization of protease activity within the tumor tissue and the tumor‐associated stroma. Strong APM activity was detectable only in the stroma of basal cell carcinoma, a result which reflects the particular tumor‐stroma interaction of this semimalignant tumor. APM activity was not detectable in either healthy epidermis or the tumor parenchyma. Altered activity of DPP IV was found in the tumor cells as well as in the surrounding connective tissue: precancerous dermatoses and basal cell carcinomas had higher levels of DPP IV‐activity than normal skin or benign seborrheic keratosis. Poorly differentiated malignant squamous cell carcinomas, however, showed no histochemically detectable DPP IV‐activity at all. This result is in line with reports of decreased activity of this enzyme in cases of malignancy.

High prevalence of seborrhoeic dermatitis on the face and scalp in mountain guides.

Background: High incidence rates of seborrhoeic dermatitis (SD) have been reported in HIV-infected individuals, indicating immunosuppression to be involved in the pathogenesis. Objective: To establish the prevalence of SD in mountain guides who have a high occupational exposure to solar UV radiation. Patients and Methods: In November 1999, 283 mountain guides were physically examined on the face and scalp for symptoms of SD in Austria (n = 75), Switzerland (n = 123) and Germany (n = 85); they were 21.3–93.1 years of age (median age 41.4 years). Results: Forty-six of 283 (16.3%) mountain guides when examined clinically were found to have SD. The median age of mountain guides with SD was 41.2 years. There were similar incidence rates in all three countries. Conclusion: SD affects mountain guides in a clearly higher percentage as the general population. We suggest UV-induced immunosuppression due to occupational sun exposure as a pathogenetic factor.

Granulomatous mycosis fungoides : Report of a case with some histopathologic features of granulomatous slack skin

We describe a case of granulomatous mycosis fungoides, tumor stage, mimicking sarcoidosis in an 82-year-old man with a 2-year history of skin disease. The final diagnosis was established after one of seven biopsy specimens showed a nongranulomatous histologic picture of patch-stage mycosis fungoides. Monoclonality was proven for the lymphocytic population by T-cell-receptor rearrangement studies. The unusually extensive granulomatous inflammation with huge giant cells surrounded by CD1a-positive cells in the other six biopsy specimens was suggestive of the histopathology of granulomatous slack skin, another rare granulomatous cutaneous T-cell lymphoma. Because both a clinical and histologic overlap between granulomatous mycosis fungoides and granulomatous slack skin have been reported in the literature, we conclude that they may belong to the spectrum of a single disease.

Destruction of tumour parenchyma in basal cell carcinoma by tumour‐associated neutral proteases: a histochemical study

Proteolytic activity was demonstrated histochemically in frozen sections of basal cell carcinomas (BCCs). After incubation of tissue sections in 0.1 m phosphate buffer with 0.25 m NaCl the tumour epithelium was almost completely destroyed. The basal and squamous cell layers of the disintegrated to varying degrees, particularly where they were directly in contact with tumour epithelium. Serine and metalloprotease inhibitors diminished this tissue destruction, lodoacetate enhanced tumour destruction, urea and potassium thiocyanate even more so. The high proteolytic activity of BCC demonstrated in this study may be an important factor in the proliferative, invasive and destructive behaviour of this tumour.

Nachsorge bei Melanompatienten

Sich sorgen um Patienten nach einer Melanomopera ration ist notwendig. Wenn bei Patienten eine lokoregionare Metastasierung eintritt, so haben sie eine Zehnjahresuberlebensrate von 20–40%, so das eine klinische und apparative Diagnostik (v.a. Lymphknotensonographie) im Rahmen der Nachsorge sinnvoll erscheint. Allerdings stirbt nach wie vor jeder 3. bis 4. Patient an den Folgen seines Melanoms.