Edgar Rieger

Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid: An alternative treatment modality for solar keratoses, superficial squamous cell carcinomas, and basal cell carcinomas?

BACKGROUND Topical photodynamic therapy with endogenous porphyrins consists of irradiation of a tumor with visible light after the application of exogenous 5-aminolevulinic acid. OBJECTIVE To assess the effectiveness of this modality, patients with precancerous conditions and various skin cancers were treated. METHODS Thirteen patients with 70 skin lesions were enrolled. Standard treatment involved the topical application of 20% 5-aminolevulinic acid in an oil-in-water emulsion. The emulsion was applied under an occlusive dressing for 4 to 8 hours before exposure to photoactivating light. RESULTS We observed a complete response after a single treatment for all 9 solar keratoses, 5 of 6 early invasive squamous cell carcinomas, and 36 of 37 superficial basal cell carcinomas. Only 1 of 10 nodulo-ulcerative basal cell carcinomas completely resolved. Eight cutaneous metastases of malignant melanoma were therapeutic failures. CONCLUSION Topical photodynamic therapy with endogenous porphyrins is effective for superficial epithelial skin tumors.

Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large cell lymphoma

Mycosis fungoides (MF) can progress to a large-cell malignant lymphoma (LCL). This transformation is associated with a more aggressive biologic behavior and course. We reviewed cutaneous tumors of 36 MF patients and divided them into two groups, one showing histologic evidence of transformation into LCL, another characterized by infiltrates of small- to medium-sized cerebriform cells (nontransformed cases). Biopsies of patches or plaques from early MF stages were available from 34 patients. Twenty of the 36 cases (55.6%) showed transformation to a large-cell variant: nine tumor-stage (T) medium-sized and large-cell pleomorphic, five T immunoblastic, two T large-cell anaplastic, and four unclassified T LCL. Sixteen cases represented nontransformed tumor stage MF. In 23 cases, including both nontransformed (n = 6) and LCL (n = 17) groups, immunohistochemical investigations revealed aberrant patterns of antigen expression (partial loss of one or more T cell-associated antigens) and the presence of activation- and proliferation-associated antigens. Clusters of B-lymphocytes formed a distinctive component of the infiltrate in two nontransformed and nine LCL biopsies. Although survival rates after tumor onset did not significantly differ between the two groups (5-year survival rate 23% for nontransformed patients, 11.1% for LCL patients, p < 0.05), overall survival from first biopsy diagnostic of MF showed a statistically significant difference between patients with nontransformed tumor stage MF compared with LCL patients (10-year survival rate 46.6% and 11.2%, respectively, p < 0.02). The recognition of transformation to LCL in MF should provide a better assessment of future therapeutic approaches.

Diagnostic Reliability of Dermoscopic Criteria for Detecting Malignant Melanoma

Background: Recently a new standardized terminology in dermoscopy has been provided by a Consensus Meeting held by the Committee on Analytical Morphology of the Arbeitsgemeinschaft

Reactive angioendotheliomatosis or intravascular histiocytosis? An immunohistochemical and ultrastructural study in two cases of intravascular histiocytic cell proliferation.

Two elderly women with complex medical histories presented with erythematous patches, in one case involving the face and forearms, and in the other both elbows. Punch biopsies from both patients revealed intravascular proliferations of medium‐sized and large cells with luminal occlusion typical of angioendotheliomatosis. Immunostaining did not show either lymphocytic or endothelial cell antigens but was consistent with a histiocytic differentiation of the intravascular cells in both cases, and was further substantiated by ultrastructural examination in one case. One patient received a course of cyclophosphamide therapy over 15 days. Skin lesions faded but did not disappear. The patient died 10 months later from cardiac and renal failure, which was most probably unrelated to the skin lesions. In the other case, lesions diminished but did not entirely resolve with treatment with low doses of oral prednisone. Angioendotheliomatosis can be divided into a malignant variant, which is an angiotropic lymphoma mostly of B‐cell phenotype, and a benign, reactive variant, which is characterized by a proliferation of cells expressing endothelial cell markers. Only one case of angioendotheliomatosis with cells of histiocytic differentiation has been published previously under the name of intravascular histiocytosis. Our cases are very similar to the latter. The question arises as to whether intravascular histiocytic cell proliferation is a neoplastic proliferation of histiocytes or an early stage of classic reactive angioendotheliomatosis representing the residual cells associated with organization of microthrombi, which will be later followed by endothelial cell proliferation.

Influence of skin tension and formalin fixation on sonographic measurement of tumor thickness

BACKGROUND High-resolution sonographic measurement of skin tumors, especially of malignant melanomas, allows presurgical assessment of the most important prognostic factor--tumor thickness. A good correlation between ultrasonographic and histopathologic thickness measurement has been reported. Procedures for preparing tissue for histopathologic examination, such as excision, fixation in formalin, dehydration in alcohol, and embedding in paraffin, may cause the tissue to retract and shrink and may therefore affect thickness measurement results. OBJECTIVE Our purpose was to evaluate the influence of skin preparation procedures on ultrasound measurement results and to compare tumor thickness values obtained sonographically versus those obtained histopathologically. METHODS Sixty-three epithelial (n = 37) and melanocytic (n = 26) tumors, benign as well as malignant, were measured by ultrasound before and immediately after excision and after overnight fixation. Sonographically and histopathologically determined tumor thicknesses were compared. RESULTS Loss of skin tension after excision led to an increase in measured tumor thickness because of spherical retraction of the specimen. Subsequent fixation, dehydration, and embedding reversed this effect, so that altogether, histopathologically assessed tumor thickness was only slightly lower than ultrasound-derived thickness before excision. This was true for melanocytic as well as epithelial lesions. CONCLUSION Loss of skin tension after excision and tissue preparation procedures seem to offset each other and lead to a good overall correlation between ultrasonographic and histopathologic measurements.

Melanotic macules following Blaschko's lines in McCune-Albright syndrome

Summary Hyperpigmented macules are a characteristic feature of neurofibromatosis and the McCune‐Albright syndrome. Whereas neurofibromatosis 1 has an autosomal dominant mode of inheritance, it has been suggested that McCune–Albright syndrome is the result of a lethal gene surviving by mosaicism. Recent molecular studies have supported this concept by providing evidence of a somatic mutation of the gene encoding the G protein. We report two patients with McCune–Albright syndrome whose melanotic macules show a clear relation to the lines of Blaschko. The lines of Blaschko are thought to represent the dorso‐ventral outgrowth of two different cell populations during embryogenesis, thus reflecting genetic mosaicism. A survey of published photographs of patients with McCune–Albright syndrome in the literature revealed additional cases with macules following Blaschkos lines. In other cases, the configuration of the macules was reminiscent of the flag‐like rectangular pattern of pigmentation found in human chimaeras. A very early somatic mutation may have similar effects on the pigmentation pattern as a chimaeric state, which is the result of the double fertilization of an ovum. Café‐au‐lait spots in 10 of our own patients with neurofibromatosis 1 could not be associated with either Blaschkos lines or the rectangular pattern of pigmentation in chimaeras. We conclude that, in contrast with the calé‐au‐lait spots in autosomal dominant neurofibromatosis 1. the configuration pattern of melanotic macules in McCune–Albright syndrome in many cases characteristically reflects the mosaic state of the organism.

Analysis of the 14;18 translocation in cutaneous lymphomas using the polymerase chain reaction.

A series of 25 cutaneous B‐cell lymphoid proliferations was analyzed for the presence of the (14;18) translocation using the polymerase chain reaction, functional sequences of rearranged chromosomes 14 and 18 were amplified in vitro, and t (14;18) specific sequences were detected in 1 of 14 primary cutaneous B‐cell lymphomas, in 1 of 14 primary nodal B‐cell lymphomas and in none of 3 B‐cell pseudolymphomas. These results indicate that the t (14;18) may occur in a small subset of primary cutaneous lymphoma. However, the difference in incidence of the t (14;18) between primary nodal and primary cutaneous lymphomas suggests that different molecular mechanisms are involved in the pathogenesis of these lymphomas.

Vaginal yeast colonization and promiscuity. A study of 197 prostitutes.

Summary. In order to study the role of promiscuity in yeast colonization of the vagina we examined vaginal smears of 197 prostitutes. Forty‐two (21%) showed yeast infection on culture, and Candida albicans was isolated in 93% of these cases. This rate is comparable to the rates in reports of large series of non‐promiscuous women in the literature and does not suggest that promiscuity alone is a predisposing factor for vaginal yeast carriage. The rate of Candida infections was approximately the same in prostitutes taking oral contraceptives as in those not taking the pill (22 and 21%, respectively; P<0.05). The prevalence of vaginal yeast colonization, however, was significantly higher in prostitutes under the age of 31 (30%) as compared with those over 30 (10%; P<0.002), thus suggesting that women in the third decade of life are more prone to vaginal Candida infections than older age groups.

Does surgical removal of primary melanoma trigger growth of occult metastases? An analytical epidemiological approach

background In several human tumor systems a potential role of surgical removal of the primary tumor upon metastatic tumor growth has been evaluated, as it has been in experimental models. The present study addresses the question of whether the removal of primary melanomas disinhibits growth of metastatic disease and results in more rapid progression. methods In a data set of 1224 primary cutaneous melanomas the risk of “thin” melanomas to present metastases within 1 year was compared with the risk of matched pairs of “thick” melanomas to present metastases at the time of diagnosis. For this purpose, a pairwise matching procedure based on certain assumptions as to tumor volume and tumor doubling time has been applied. results When a long tumor doubling time is assumed (200, 400, or 800 days), the tumors removed seem to have a significantly higher risk of metastases to become clinically apparent within 1 year titan the matched pairs of tumors to present metastatic disease at the time of diagnosis (chi‐square < 0.01). When short tumor doubling time is assumed (50 or 100 days), the difference is not significant, but there also seems to be no benefit far the operated patients. conclusion In the present data set there is evidence that surgery of primary melanoma man enhance tumor growth at metastatic sites.

Expression of cytoskeletal components in melanocytic skin lesions. An immunohistochemical study.

The cytoskelelon is considered to he important for maintaining cell shape and facilitating cell movement. In the present study, the expression of cyloskeletal components is examined in benign and malignant mclanocytic skin tumors. Paraffin sections of 75 cases (25 each of nevocel-lular nevus, primary malignant melanoma, and cutaneous melastascs of malignant melanoma) were stained with antibodies to tubulin. myosin. actin. and vimentin using a three-step immunopcroxidasc method. The staining results were assessed independently for tumor cells and stroma cells in comparison to inbuilt reference structures. Vimentin is found in all melanocytic lesions in the tumor as well us in the stroma cells. In malignant lesions, the tumor cell staining intensity varies between neighboring regions: particularly in malignant melanoma the staining is pronounced in the tumor periphery (X2 test: p < 0.05). Actin is only weakly positive in nevus cells and primary melanoma tumor cells, but strongly expressed in meta-static tumor cells (p < 0.001). Nevus fibroblasts are only weakly positive, whereas the stroma fibroblasts in the malignant lesions are strongly positive (p < 0.001). The same is true for myosin and tubulin expression in dermal fibroblasts (p < 0.001). whereas the tumor cells are equally (weakly) positive in all mclanocytic lesions. Our study shows that there are significant differences in the immunohistochcmical expression of cytoskeletal components in various melanocytic tumors. There is an elevated expression of vimentin and actin in the tumor cells, particularly of mctasiatic lesions. However, the most pronounced differences arc found in the dermal fibroblasts. The increased expression of actin. myosin. and tubulin in the fibroblusts of malignant melanocytic tumors suggests an active contribution of stroma cells in the growth of malignant tissues, probably due to stimulation by the tumor cells.