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H Kerl

Publications and source records attributed to H Kerl.

At least 145 records · Page 8Linked to original sources

Pathological findings suggestive of interclonal stabilization in a case of cutaneous melanoma.

Metastatic spread is a complex process based on manyfold interactions of the tumor cells with each other and with the surrounding stroma. In experimental systems tumor cell heterogeneity and presence of various subpopulations which interact with one another to stabilize their relative proportions within the population has been shown. Here we report a patient with melanoma, showing morphological evidence of two distinct tumor cell populations in the primary tumor and in all subcutaneous metastases. By image analysis, both populations were clearly characterized by minimal nuclear diameter and by nuclear form factor and were demonstrable in each specimen. The fact that these peculiar cell populations were present in all melanoma lesions removed from the patient might indicate that the populations require the presence of each other and that none of them is metastatically competent on its own.

Cell Division↗

Different treatment modalities for the management of a patient with the nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma (BCC) syndrome is a genetically linked disorder characterized by multiple BCCs associated with various skeletal abnormalities and sometimes with mental retardation. Because of the large number of lesions, treatment of BCCs in these patients may be extremely difficult. The value of different therapeutic options was assessed in a patient with multiple, disfiguring nevoid BCC syndrome. Surgical excision and split-skin grafting was used to remove three larger tumors. Photodynamic therapy led to healing of flat lesions; small papules within the treated areas, however, did not respond to this type of management. Three nodular BCCs treated with intralesional application of interferon alfa-2b were markedly reduced in size. Still, complete healing could not be achieved. Nodular lesions vaporized with the CO2 laser disappeared and showed no recurrence after 2 years of follow up. Our experience indicates that CO2 laser vaporization of BCCs allows the treatment of a large number of lesions in a single session, and is indicated when surgical treatment is not feasible for all lesions. Photodynamic therapy with 5-amino-levulinic acid may be a valid therapeutic option for flat lesions only. Intralesional application of interferon alfa-2b removes papular lesions of small size.

Aged↗

Photoaccentuated erythroderma associated with CD4+ T lymphocytopenia: successful treatment with 5-methoxypsoralen and UVA, interferon alfa-2b, and extracorporeal photopheresis.

We describe a 53-year-old HIV-negative white man who had chronic CD4+ T lymphocytopenia and photoaccentuated erythroderma with lymphoma-like histologic changes. The erythroderma completely responded to 5-methoxypsoralen and UVA (PUVA), interferon alfa-2b, and extracorporeal photopheresis. During therapy opportunistic skin infections, including tinea corporis, warts, and disseminated molluscum contagiosum, developed. Although the patient met the current definition of idiopathic CD4+ T lymphocytopenia (ICTL), we cannot rule out the possibility that this peripheral CD4+ T lymphocytopenia resulted from sequestration of CD4+ T lymphocytes in erythrodermic skin.

5-Methoxypsoralen↗

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.

Adolescent↗

Morphological stages of pilomatricoma.

In 1983, Ackerman proposed that pilomatricoma represents an infundibular-matrix cyst in its early stages. To study the evolution of this cystic neoplasm, we examined 118 lesions from 116 patients with pilomatricoma histopathologically and categorized the lesions into four distinct and chronological stages: early, fully developed, early regressive, and late regressive. Early lesions (eight cases) were small cystic structures lined by squamoid and basaloid epithelium containing keratin filaments and faulty hair matrix material composed of shadow cells. Fully developed lesions (27 cases) were large neoplasms lined by basaloid epithelium at their periphery, and within, composed of irregularly shaped, densely packed zones of cornified masses containing shadow cells. Early regressive lesions (37 cases) had no apparent epithelial lining but did have basaloid cell foci at the periphery; within, they were composed of pink hair matrix material with shadow cells surrounded by granulation tissue with inflammatory infiltrate and multinucleated histiocytic giant cells. Late regressive lesions (42 cases) had no epithelial component and were composed of irregularly shaped, partially confluent masses of faulty hair material, and calcified (and sometimes metaplastically ossified) shadow cells embedded in a desmoplastic stroma, with little or no inflammatory infiltrate. In four cases, there was a relatively large dermal nodule composed of several interconnected lobules that consisted largely of basaloid cells with only a few areas of shadow cells. We interpreted these lesions as proliferating pilomatricomas. Based upon our histopathologic findings, we propose that pilomatricomas may be categorized into four distinct morphological stages and that these stages reflect the "life" of a pilomatricoma. Thus, the lesion begins as an infundibular matrix cyst and ends up as a calcified and ossified nodule with no visible epithelial component.

Adolescent↗

Quantitative morphology of collagen fibers in cutaneous malignant melanoma and melanocytic nevus.

Since tumor growth and metastastatic spread are considered to depend on tumor-stroma interaction, the present study describes the architecture of collagen fibers in 12 cases each of primary melanoma (vertical tumor thickness > 1 mm) and common melanocytic nevi in azan-stained sections by using automated image analysis. In each case, at least 100 high-power fields were consecutively sampled from the tumor center, the tumor periphery, and the surrounding normal-appearing reticular dermis. In both diagnostic groups, collagen density (amount of collagen per tissue volume) and mean collagen fiber bundle diameter was significantly lower in the tumor periphery than in the surrounding stroma and again lower in the tumor center than in the tumor periphery. When melanomas and nevi were compared with each other, melanomas had fewer, but thicker, collagen bundles than did nevi, particularly at the tumor periphery. Taking the mean values of each case as classifiers in multivariate logistic regression analysis, 21 of 24 cases were correctly classified (chi-squared test, p < 0.0001), indicating that the parameters of collagen architecture at least in part reflect biological differences between benign and malignant melanocytic skin lesions.

Adult↗

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: a clinicopathologic and prognostic study of 42 patients.

The clinical and histopathologic features of specific skin infiltrates in patients with B-cell chronic lymphocytic leukemia (B-CLL) have rarely been reported in detail. In this study we analyzed the clinical, histopathologic, immunophenotypic, and molecular features of 84 skin lesions from 42 patients (M:F = 1.3:1; mean age, 66.0 years; range, 42-83 years) with specific cutaneous manifestations of B-CLL. The duration of B-CLL before skin manifestations varied from 0 to 142 months (mean, 39 months). In seven patients (16.7%), skin lesions represented the first sign of disease. Clinical presentations included localized or generalized erythematous papules, plaques, nodules, and large tumors. Ulceration was uncommon. In six patients lesions were confined at the sites of scars from previous herpes zoster (four patients) or herpes simplex (two patients) eruptions. Histologically, three main patterns were recognized: (a) patchy perivascular and periadnexal, (b) nodular-diffuse, and (c) band-like. Cytomorphologically, small monomorphous lymphocytes predominated. Proliferation centers were observed in only four specimens. In two patients presenting with tumors, a high content of large cells with feature of centroblasts and immunoblasts was found (Richter's syndrome). Immunohistologic analyses were performed on paraffin-embedded specimens in 40 biopsies from 20 patients and on cryostat sections in 17 biopsies from 11 patients. Neoplastic B lymphocytes in all cases showed an aberrant phenotype (paraffin sections: CD20+/CD5+/CD43+; cryostat sections: CD19+/CD5+; immunoglobulin light-chain restriction). Proliferation markers (Ki67, PCNA, MIB1) stained 5 to 80% of cells (mean, 25%; median, 20%). Polymerase chain reaction performed in nine cases on paraffin-embedded tissues using consensus primers for immunoglobulin heavy-chain genes showed a monoclonal population of B lymphocytes in all cases. Several discrete bands in addition to the prominent ones were noted in five cases, indicating the additional presence of B lymphocytes whose immunoglobulin genes were not monoclonally but oligoclonally rearranged. Follow-up data could be obtained from 31 patients. The two patients with Richter's syndrome died after 5 and 8 months, respectively. The 5-year survival of patients with small-cell cutaneous B-CLL was 66.6%. Our study indicates that cutaneous specific manifestations of B-CLL present with characteristic histologic, immunophenotypic, and molecular patterns. Prognosis in these patients is probably not affected by skin involvement.

Adult↗

The role of MT2 and anti-bcl-2 protein antibodies in the differentiation of benign from malignant cutaneous infiltrates of B-lymphocytes with germinal center formation.

MT2/CD45RA and anti-bcl-2 protein (Bcl-2) monoclonal antibodies are useful markers in distinguishing follicular lymphomas from reactive follicular hyperplasia of the lymph nodes. We examined biopsy specimens from 11 patients with primary cutaneous B-cell follicle center lymphomas, 10 patients with cutaneous pseudolymphomas with germinal centers, and 6 patients with inflammatory infiltrates with germinal centers in non-lymphoid cutaneous tumors (3 basal cell carcinomas, 2 malignant melanomas, and 1 solar keratosis), in order to evaluate the utility of MT2 and anti-Bcl-2 antibodies in differentiating benign from malignant germinal center cell proliferations in the skin. Immunohistochemical evaluation of MT2 and Bcl-2 was focused exclusively on the reactivity of germinal center cells. Specific membranous MT2 positivity was found in 2/11 cutaneous follicle center lymphomas; a diffuse, non-specific staining pattern was identified in 3/11 follicle center lymphomas and in 1/6 inflammatory infiltrates in non-lymphoid tumors. A negative MT2 reaction was observed in 6/11 follicle center cell lymphomas, in all cases of pseudolymphomas and in 5/6 inflammatory infiltrates in non-lymphoid tumors. Bcl-2 positivity was detected only in 1/11 follicle center lymphomas. Germinal center cells in all other cases were Bcl-2 negative. Our results suggest that MT2 and anti-Bcl-2 antibodies are only of limited value in differentiating primary cutaneous follicle center lymphomas from cutaneous pseudolymphomas with germinal centers.

Antibodies, Monoclonal↗

Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia.

The relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42-83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or bandlike (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p < 0.01; z = 5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.

Adult↗

Clinical and histological features of poor prognosis in cutaneous metastatic melanomas.

Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell-stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n = 59) and lesions from patients with a longer survival (n = 285). Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1 +/- 14.1 years versus 58.8 +/- 15.3 years), had developed earlier after the primary tumor (mean time of 21.7 +/- 19.9 months versus 43.3 +/- 27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p < 0.001) and PRECOLL (82.8% versus 57.6; p < 0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p < 0.01) and PREFAT (68.1% versus 46.8%; p < 0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen. In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.

Adult↗

Detection of Borrelia burgdorferi-specific DNA in urine specimens from patients with erythema migrans before and after antibiotic therapy.

A nested PCR was developed for the detection of Borrelia burgdorferi-specific DNA in the urine of patients with erythema migrans. The target for the nested PCR was a specific region of the flagellin gene; the detection limit was less than five organisms of B. burgdorferi including all three species B. burgdorferi sensu stricto, B. afzelii, and B. garinii. A prospective, controlled, blinded study was performed with 26 patients with erythema migrans to evaluate the nested PCR method with clinical samples. B. burgdorferi-specific DNA could be detected in urine specimens from 22 of 24 patients with erythema migrans (sensitivity, 91.61%). Immediately after therapy, 11 of 19 patients still yielded positive results (58%). Eight weeks after therapy, 2 of 16 patients (13%) were positive by PCR of urine, and 20 weeks after treatment none of seven investigated urine samples was reactive. Essential for the sensitivity that was obtained was the development of a simple DNA extraction procedure. The results of the study indicate that the described method is highly sensitive and allows for the effective control of the efficacy of antibiotic therapy in patients with early Lyme borreliosis.

Adult↗

Acrodermatitis chronica atrophicans in an 11-year-old girl.

We report a case of acrodermatitis chronica atrophicans in an 11-year-old girl living in an area endemic for Lyme borreliosis. The diagnosis was first made on the basis of clinical, histopathological and serological findings. Moreover, Borrelia burgdorferi-specific DNA was amplified from lesional skin by polymerase chain reaction. Intravenous treatment with ceftriaxone (2 g once daily) for 2 weeks was initiated. The skin changes clearly responded to the therapy, and Borrelia burgdorferi-specific gene segments were no longer detectable by polymerase chain reaction. This is the first report of molecular-proven acrodermatitis chronica atrophicans in childhood. The occurrence of this late skin manifestation of Lyme borreliosis in children is reviewed.

Acrodermatitis↗

Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia arising at the site of herpes zoster and herpes simplex scars.

BACKGROUND: Cutaneous lymphoid infiltrates at sites of herpes zoster scars in patients with B-cell chronic lymphocytic leukemia (B-CLL) often are diagnosed as benign lymphoid hyperplasia ("pseudolymphomas"). The histologic and immunophenotypic features of these lesions are not well characterized. Appearance of skin lesions in B-CLL patients is considered a poor prognostic sign. METHOD: Eight punch biopsies from five patients (three males, two females; mean age, 66.7 years) affected by B-CLL and presenting with lesions at sites of previous herpes simplex (upper lip, one patient) or herpes zoster (trunk, four patients; forehead, one patient) infections were included in the study. Histologic examination was performed on routine sections stained with hematoxylin and eosin and Giemsa. Immunohistologic stainings were performed with a standard three-step immunoperoxidase technique on formalin fixed, paraffin embedded tissue sections. RESULTS: Specific cutaneous infiltrates of B-CLL were diagnosed histopathologically and immunophenotypically in eight biopsies from all five patients. Clinically, patients presented with erythematous papules or plaques confined to the area of previous herpes virus eruptions. Histopathologic features in most cases were characterized by a variably dense perivascular and periadnexal infiltrate of small hyperchromatic lymphocytes throughout the entire dermis, reaching the subcutaneous fat. In one case, a dense, diffuse infiltrate involving the entire dermis was observed. A granulomatous reaction with presence of epithelioid and multinucleated giant cells was a prominent feature in four biopsies from three patients. Light areas containing large lymphoid cells with features of prolymphocytes and paraimmunoblasts (so-called "proliferation centers") could be observed only in the case characterized by a diffuse infiltrate. Immunohistology revealed an aberrant CD20+/CD43+ phenotype of neoplastic B cells, which is not found in normal B lymphocytes (CD20+/CD43-). Reactive T lymphocytes were present in all lesions and had a normal CD20-/CD43+/CD45Ro+ phenotype. At the time of this writing, four patients were alive without signs of skin disease after a mean follow-up of 58.5 months, and one patient died of B-CLL 24 months after the cutaneous eruption. CONCLUSIONS: Specific cutaneous infiltrates of B-CLL are not uncommon at sites of herpes virus scars. The diagnosis can be confirmed by histopathologic and immunophenotypic criteria. The prognosis is better than previously reported.

Aged↗