Confocal laser scanning microscopy as a new valuable tool in the diagnosis of onychomycosis - comparison of six diagnostic methods.

Onychomycosis is common and can mimic several different nail disorders. Accurate diagnosis is essential to choose the optimum antifungal therapy. The aim of this study was to evaluate the use of confocal laser scanning microscopy (CLSM) and optical coherence tomography (OCT) as new non-invasive diagnostic tools in onychomycosis and to compare them with the established techniques. In a prospective trial, 50 patients with suspected onychomycosis and 10 controls were examined by CLSM and OCT. Parallel KOH preparation, culture, PAS-staining and PCR were performed. PCR showed the highest sensitivity, followed by CLSM, PAS and KOH preparation. OCT offered the second best sensitivity but displayed the lowest specificity. CLSM and KOH preparation showed a high specificity and CLSM offered the best positive predictive value, similar to KOH preparation and OCT. Fungal culture showed the lowest sensitivity and the worst negative predictive value, yet culture and PCR are the only techniques able to identify genus and species. In summary, CLSM was comparable to PAS staining and superior to KOH preparation. Due to the low specificity we assess OCT not as appropriate. In the differentiation of species PCR outplays the fungal culture in terms of time and sensitivity.

[Muir-Torre syndrome with previously undescribed frameshift mutation in the MSH2 gene]. / Muir-Torre-Syndrom mit bisher nicht beschriebener Frameshift-Mutation im MSH2-Gen.

Muir-Torre syndrome (MTS) is a rare phenotypic variant of hereditary non-polyposis colorectal carcinoma (HNPCC, Lynch syndrome), in which patients, in addition to visceral carcinomas, develop skin tumors. Multiple keratoacanthomas and basal cell carcinomas with sebocytic differentiation are characteristic as well as multiple benign and malignant tumors of the sebaceous glands, such as sebaceous adenoma, sebaceous epithelioma (sebaceoma) and sebaceous carcinoma. Particularly Cystic tumors of the sebaceous glands are especially suggestive of MTS. In genetically predisposed persons, cutaneous and visceral tumors are diagnosed at an average age of 53 years. Here we present an interesting case of a 65-year-old man in whom molecular genetic tests revealed a novel mutation in the MSH2 gene, leading to a frame shift within the gene.

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.

[Melanoma. Results with "sentinel node" sampling]. / Melanom. Ergebnisse mit dem "Sentinel node".

Since June 1995 we have practised a gamma probe guided sentinel lymphadenectomy (SLNE) in 274 patients after injecting a colloidal 99 m-Tc labelled solution around the tumor. By this technique the detection and excision of the SLN succeeded in 99.3% of all cases. We found micrometastases in about 53.1% of patients with pT3 and pT4 melanomas. The specimen of the radical lymph node dissection contained in 30% further metastases. A regional recurrence after SLNE occurred only in one case, a SLN-negative patient.

Sentinel lymphonodectomy in nonmelanoma skin malignancies.

BACKGROUND: Whereas the value of sentinel lymphonodectomy (SLNE) in malignant melanoma is established, experience with SLNE in nonmelanoma skin cancers is limited. OBJECTIVES: The feasibility of SLNE in nonmelanoma skin tumours is evaluated. METHODS: Thirty-seven patients with high-risk nonmelanoma skin tumours underwent SLNE: 11 squamous cell carcinomas (SCCs), seven Merkel cell carcinomas (MCCs), five cutaneous lymphomas, eight adnexal carcinomas and six other skin cancers, all clinical stage N0. RESULTS: In nine patients (four MCCs, two SCCs, three lymphomas) the sentinel lymph nodes (SLNs) showed histological evidence of microinvolvement. In five of these nine patients, radical lymph node dissection (RLND) was performed, revealing further micrometastases in three patients (two SCCs, one MCC). No patient with negative SLN showed tumour dissemination during the follow-up over a mean of 2.5 years (range 2 months to 4.5 years, median 2.4 years). CONCLUSIONS: Our data provide evidence that SLNE is a minimally invasive and highly sensitive staging tool in selected patients with high-risk nonmelanoma skin cancers.

[Erythema necrolyticum migrans after rectal adenocarcinoma]. / Erythema necrolyticum migrans nach Rektumadenokarzinom.

Necrolytic migratory erythema (NME) is mostly associated with a pancreatic-A-cell-glucagonoma and is considered to be a well-defined cutaneous paraneoplastic syndrome. We report on a 74-year old female who atypically developed a NME after surgical treatment of a rectal adenocarcinoma. Continuous staging and laboratory investigation over four years gave no evidence of any metastasis or further neoplasia.

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).

Prognostic and therapeutic implications of sentinel lymphonodectomy and S-staging in Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine neoplasm of the skin with a high propensity for early lymph node metastasis and subsequent distant spread. Optimal treatment and prognostic factors are poorly defined. OBJECTIVE: The purpose of this study is to assess the prognostic and therapeutic relevance of sentinel lymphonodectomy in MCC. METHODS: Five patients with biopsy-proven MCC underwent gamma-probe-guided sentinel lymphonodectomy assisted by lymphatic mapping. From each sentinel lymph node (SLN), a series of paraffin sections was histologically and immunohistochemically examined for the presence of micrometastases, which were then staged according to the recently published S classification. RESULTS: Four of the 5 patients showed metastatic disease in the SLNs, 3 of which were classified as S(2), 1 as S(3). Only 1 of the S(2) patients demonstrated additional positive nodes at completion lymphonodectomy. The patient staged as S(3) refused a radical lymph node dissection and died within 1 year due to widespread metastasis. CONCLUSIONS: Sentinel lymphonodectomy is a low-morbidity procedure which enables an early detection and exact staging of regional lymph node metastases with potentially high prognostic and therapeutic relevance in MCC.

Characterization of synovial macrophages by monoclonal antibodies in rheumatoid arthritis and osteoarthritis.

Inflamed synovium in rheumatoid arthritis (RA) and activated (inflammatory) osteoarthritis (aOA) sometimes demonstrates close similarities in routine histology. If the clinical findings are ambiguous, too, differentiation may become difficult, and the only diagnosis is "chronic unspecific synovitis". By immunohistologic staining with monoclonal antibodies of the Ki-M-series directed against cells of the monocyte/macrophage lineage semiquantitative evaluation of tissue samples is possible thus gaining helpful results for the differential diagnosis. There are significantly more macrophages in RA than in aOA especially in the synovial lining. Proliferating and activation markers also show slight but significant augmentation (OKT9) in RA.

Secondary lymph node involvement from primary cutaneous large B-cell lymphoma of the leg: sentinel lymph nodectomy as a new strategy for staging circumscribed cutaneous lymphomas.

BACKGROUND: Primary cutaneous large B-cell lymphoma of the leg (LBCLL) is a recently defined type of non-Hodgkin's lymphoma. It forms a separate category in the new classification of primary cutaneous lymphomas elaborated by the European Organization for Research and Treatment of Cancer. It is associated with a less favorable prognosis than the most frequently occurring types of primary cutaneous B-cell lymphoma. METHODS: The authors present four patients with the typical clinicopathologic constellation of LBCLL. Three of them died during the years 1993-1996. The authors reviewed their courses. The fourth patient was staged by sentinel lymph nodectomy (SLNE), i.e., the selective surgical removal and histologic examination of the first draining lymph node associated with the cutaneous tumor. RESULTS: The courses of the three previous patients were characterized by secondary involvement of regional lymph nodes followed by systemic dissemination of the lymphoma in a third step. Although the conventional staging of the fourth patient had been negative for any extracutaneous lymphoma manifestation, the SLNE revealed initial regional lymph node involvement, which had decisive implications for the choice of therapy. CONCLUSIONS: SLNE may gain a prominent role in the staging of circumscribed cutaneous lymphomas, in addition to its already established position in melanoma management. Further positive effects of SLNE are 1) better distinction of primary cutaneous lymphomas with secondary lymph node involvement from primary lymph node lymphomas with skin manifestation, and 2) better insight into the biology of different primary cutaneous lymphoma types.

A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma.

BACKGROUND: The sentinel lymph nodes (SLNs) as the primary targets for lymphatic metastases can be removed selectively by gamma probe-guided sentinel lymph nodectomy (SLNE) in nearly all patients with cutaneous melanoma. Correspondingly high standards in terms of specificity, sensitivity, and microstaging are required for the evaluation of SLNs. METHODS: Since 1995, the authors have performed SLNE in 389 lymph node regions (LNRs) on 342 patients with melanoma. The harvested 636 SLNs and a further 1394 nonsentinel lymph nodes (non-SLNs) were evaluated by standardized, semiserial section histology, including immunohistochemistry. For each LNR, this technique permitted routine S classification using two simple morphometric parameters: the number of tumor-involved, 1-mm slices of the SLNs (n) and the centripetal depth of metastatic cell invasion (d). S1 was defined by 1 < or = n < or = 2 and d < or = 1 mm, equivalent to localized peripheral tumor cell deposits; S2 was defined by n > 2 and d < or = 1 mm, indicating more extended peripheral metastases; S3 was defined by d > 1 mm in SNLs with deeper metastatic infiltration; and S0 meant no detectable tumor cells (n = 0). RESULTS: The authors diagnosed 325 SLNs as S0, 24 SLNs as S1, 22 SLNs as S2, and 18 SLNs as S3. The occurrence of at least one melanoma-positive non-SLN subsequent regional completion lymph node dissection (RCLND) significantly increased from 0 of 12 in S1 SLNs to 2 of 13 in S2 SLNs and 9 of 15 in S3 SLNs (P = 0.001; chi-square test). Like the T classification of the primary melanoma, the S classification proved to be a highly significant predictor for distant metastasis (P < 0.001). It turned out to be an independent factor of influence on distant metastasis and survival in multivariate Cox analyses, which included tumor thickness, primary tumor site, patient gender, and patient age as covariates. CONCLUSIONS: The data presented recommend the S-staging concept as a promising option to fill a gap between the T and conventional N component of the pTNM classification. If its predictive capacity can be confirmed in multicenter studies, then the S classification may become the decisive criterion for or against RCLND, and a combined T plus S staging system will help to improve prognostically relevant stratification of melanoma patients in adjuvant therapy trials.