Human herpesvirus 8-specific DNA sequences in primary cutaneous B-cell lymphomas.
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Base Composition↗
Biomedical subjects
L Cerroni
Publications and source records attributed to L Cerroni.
Ancient melanocytic nevus.
Ancient melanocytic nevus is an example of a simulator of malignant melanoma, designated ancient because it shares numerous features with ancient schwannoma. Knowledge of the histopathologic characteristics of this benign melanocytic neoplasm should enable pathologists to avoid overdiagnosis of it as melanoma arising in the intradermal portion of a nevus. Ancient nevi are found most commonly on the face of older persons. The neoplasm is usually a dome-shaped, skin-colored or reddish brown papule, usually with features of a Miescher's nevus. Histopathologically, ancient nevi are exoendophytic, mostly intradermal proliferations of two populations of melanocytes: one with large pleomorphic nuclei and the other with small monomorphous ones. The large melanocytes may resemble those of the epithelioid type of Spitz's nevus. A few mitotic figures may be present in a particular section. The epidermis usually is uninvolved, but sometimes there may be a junctional component. Other important findings are degenerative changes that include thrombi, zones of hemorrhage, pseudoangiomatous changes, thick rims of sclerosis around dilated venules, fibrosis, and mucin. Ancient nevi frequently are misdiagnosed as melanoma arising in an intradermal nevus.
Aged↗
Simulators of malignant melanoma of the skin.
Early recognition of malignant melanoma is crucial in order to remove lesions at a stage when complete cure can still be achieved. Unfortunately, however, some melanomas defy clinical and/or histopathological recognition, and some benign lesions (melanocytic or non-melanocytic) can present with clinical and/or histopathological aspects simulating malignant melanoma. Awareness of these simulators is important to avoid pointless (and potentially dangerous) aggressive treatments. In this review, we have illustrated the clinicopathological features of the most important benign simulators of malignant melanoma of the skin.
Adult↗
EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer.
Primary cutaneous lymphomas represent a heterogeneous group of T- and B-cell lymphomas that show considerable variation in histology, phenotype, and prognosis. Recently, the European Organization for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Project Group has reached consensus on a new classification for this group of diseases. The EORTC classification for primary cutaneous lymphomas is based on a combination of clinical, histologic, and immunophenotypic criteria, and thus contains well-defined disease entities rather than histologic subgroups. In addition, this new classification contains a number of provisional entities, which may display characteristic histologic features, but are not yet well defined clinically. These provisional entities account for less than 5% of all primary cutaneous lymphomas. In this report the basic principles of this new classification, as well as the characteristic features of the different disease entities, are described. In addition, survival data of 626 patients with primary cutaneous lymphomas derived from the registry of the Dutch Cutaneous Lymphoma Working Group, illustrating the clinical validity of this new classification, are presented.
Humans↗
Cutaneous localization of B-cell chronic lymphocytic leukemia at the site of varicella/herpesvirus eruptions.
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B-Lymphocytes↗
Lymphomatoid papulosis, pityriasis lichenoides et varioliformis acuta, and anaplastic large-cell (Ki-1+) lymphoma.
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Diagnosis, Differential↗
Borrelia burgdorferi-associated primary cutaneous B cell lymphoma: complete clearing of skin lesions after antibiotic pulse therapy or intralesional injection of interferon alfa-2a.
We report two patients with low-grade malignant primary cutaneous B cell lymphoma in association with Borrelia burgdorferi infection. Extracutaneous manifestations were ruled out by standard staging procedures. Infection with Borrelia burgdorferi was confirmed by cultivation from lesional skin in both patients. In the first patient skin lesions cleared completely after pulse therapy with cefotaxime, whereas in the second patient antibiotic treatment failed. In this patient, however, skin lesions completely cleared after intralesional injection of interferon alfa-2a. Antibiotic treatment or intralesional injection of interferon alfa-2a should be considered as a first-line treatment of Borrelia burgdorferi-associated primary cutaneous B cell lymphoma before more aggressive conventional therapeutic modalities (e.g., radiation therapy) are applied.
Adult↗
Primary cutaneous neuroendocrine (Merkel cell) carcinoma in association with squamous- and basal-cell carcinoma.
The co-existence of squamous-cell carcinoma (SCC) and neuroendocrine (Merkel cell) carcinoma (NEC) of the skin has been well documented in several patients. The concurrent development of NEC and basal-cell carcinoma (BCC) in the same cutaneous lesion, on the other hand, has not been reported. We describe a 68-year-old man presenting with NEC, SCC, and BCC arising at the same site in retroauricular skin. Cells of NEC and SCC showed an intermingled pattern of growth, whereas those of BCC were "embedded" among those of the other two tumors. Immunohistochemical stains were consistent with the histopathologic diagnosis. We believe that this is the first report of the association of NEC, SCC, and BCC in the same skin lesion.
Aged↗
Cutaneous leiomyosarcoma.
We report the clinical, histopathologic, immunohistologic, and prognostic findings in 19 patients with cutaneous leiomyosarcoma, eight males and 11 females (mean age, 66 years; age range, 41-93 years). The tumors presented mainly as solitary lesions and were located on the head and neck (eight lesions), trunk (four lesions), upper extremities (three lesions), and lower extremities (four lesions). Histopathologically, two predominant growth patterns were observed: nodular (12 cases) and diffuse (seven cases). Neoplasms with a nodular growth pattern were characterized by high cellularity and prominent nuclear atypia, and they showed conspicuous mitoses, several necrotic cells, and sometimes extensive necrotic areas. By contrast, most cutaneous leiomyosarcomas with a diffuse growth pattern revealed low cellularity, well-differentiated smooth muscle cells, inconspicuous mitotic figures, and few or no necrotic cells. Immunohistologic investigations revealed all cutaneous leiomyosarcomas to express vimentin and smooth muscle actin. Pan-muscle actin (HHF-35) was also expressed in most cases (15 lesions). However, only 12 lesions showed positive staining for desmin. Remarkable was the expression of cytokeratins in five lesions. Clinical follow-up revealed local recurrences in five patients (three cases with nodular pattern and two lesions with a diffuse pattern) after a period ranging from 8 months to 3 years after surgical excision. No distant metastases have been observed in our series. We conclude that cutaneous leiomyosarcoma with a diffuse growth pattern may constitute a pitfall in histopathologic diagnosis because of the presence of only subtle criteria for malignancy. Cutaneous leiomyosarcoma may show different immunophenotypes, thus emphasizing the importance of using a large panel of antibodies (smooth muscle actin, HHF-35, desmin, vimentin, cytokeratins, and S-100 protein) in immunohistologic diagnosis. Cutaneous leiomyosarcoma sometimes reveals local recurrences, but it has negligible potential for distant metastases.
Actins↗
Primary cutaneous marginal zone B-cell lymphoma: a recently described entity of low-grade malignant cutaneous B-cell lymphoma.
Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.
Adult↗
p53 mutation in squamous cell carcinomas from psoriasis patients treated with psoralen + UVA (PUVA).
Individuals suffering from psoriasis are treated with a combination of psoralen and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies have shown that PUVA therapy is a risk factor for skin cancer in psoriasis patients. Although PUVA treatment induces skin cancer in laboratory animals, it is unknown whether the increased incidence of skin cancer reported in PUVA-treated psoriasis patients is due to the carcinogenic effects of PUVA or due to other factors such as UVB. Because UV and PUVA induce different types of DNA damage resulting in unique types of p53 mutation, we investigated whether skin cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53 mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA-treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of p53 mutations occurred at 5'TpG sites. Although previous studies have shown that 5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG sites are also quite common. Interestingly, a sizable portion of p53 mutations detected were C-->T or CC-->TT transitions, characteristic of UV-induced mutations. Because some psoriasis patients had substantial exposure to UVB before PUVA therapy and because the light sources used in PUVA therapy contained small but significant wavelengths in the UVB region, it is possible that the C-->T and CC-->TT transitions detected in SCCs from PUVA-treated patients were induced by UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in the development of skin cancer in Austrian psoriasis patients who undergo PUVA therapy.
Adult↗
Leukemic cells within skin lesions of psoriasis in a patient with acute myelogenous leukemia.
We report on an 81-year-old man with acute myelo-monocytic leukemia (FAB M4) and a long-standing history of psoriasis. Biopsy of psoriatic plaques revealed the coexistence of characteristic histopathologic aspects of psoriasis together with an infiltrate of blasts with features of myelo-monocytes, suggestive of a specific leukemic infiltrate within plaques of psoriasis. Immunohistologic stainings showed positivity of blasts for LN2 (CD74), MT1 (CD43), and lysozyme, consistent with a myeloid lineage of these cells. To the best of our knowledge, this is the first report on the association of psoriasis with myelogenous leukemia. The presence of leukemic cells within psoriatic skin plaques may be explained by non-specific recruitment of recirculating malignant cells to the skin. Alternatively, as psoriasis is an inflammatory disease involving granulocytes among other cell types, it may be hypothesized that leukemic cells retain to some extent their capability to respond to physiologic stimuli and enter the skin in response to specific chemotactic factors.
Aged↗
Infection by Borrelia burgdorferi and cutaneous B-cell lymphoma.
In past years, association of primary cutaneous B-cell lymphoma (CBCL) with infection by Borrelia burgdorferi has been reported in a few patients. The evidence for a pathogenetic role was based on clinical grounds or raised titre of antibodies in serum. Both methods, however, do not prove the association between the micro-organism and the CBCL, especially in countries where infection by Borrelia burgdorferi is endemic. Moreover, the exact percentage of Borrelia burgdorferi-positive CBCL is not known. We retrieved from our files 50 cases of CBCL to perform PCR analysis of Borrelia burgdorferi DNA on paraffin-embedded tissue sections. Only patients with primary CBCL were selected. In all cases, monoclonality of the infiltrate was confirmed by immunohistological pattern of immunoglobulin light chains or molecular analysis of JH gene rearrangement, or both. Specific DNA sequences of Borrelia burgdorferi were identified in cutaneous lesions from 9 patients (follicle center lymphoma: 3/20; immunocytoma: 3/4; marginal zone B-cell lymphoma: 2/20; diffuse large B-cell lymphoma: 1/6). Specificity was confirmed by Southern blot hybridisation in all positive cases. We could show that Borrelia burgdorferi DNA is present in skin lesions from a small proportion of patients (18%) with various types of CBCL. Our results may have therapeutic implications. In analogy to Helicobacter pylori-associated MALT-lymphomas, which in some cases can be cured by eradication of Helicobacter pylori infection, a proportion of CBCL may be cured with antibiotic therapy against Borrelia burgdorferi. Although yet speculative, adequate antibiotic treatment for patients with primary CBCL should be considered before more aggressive therapeutic options are applied, particularly in countries where infection by Borrelia burgdorferi is endemic. PCR analysis of Borrelia burgdorferi DNA is a fast test that should be performed in all patients with CBCL to identify those who more likely could benefit from an early antibiotic treatment.
Biopsy↗
Laser beam microdissection in the diagnosis of cutaneous B-cell lymphoma.
Interpretation of molecular analyses of cutaneous lymphoid infiltrates may be difficult because a heterogeneous group of cells in usually present within the neoplasms. Extraction of DNA from tissue sections does not provide exact information about which cell population has been analysed. We present a laser microscope system that allows selective molecular analysis of single cells or small groups of cells in cases of cutaneous lymphoma. An ultraviolet (UV)-laser microscope system (PALM, Wolfratshausen, Germany) was used to isolate particular populations of cells from a routinely processed specimen of a cutaneous follicular lymphoid proliferation. Using the UV-laser beam, a circle was cut around a target germinal centre in order to separate it from neighbouring tissues and to isolate a pure population of germinal centre cells. Isolated cells were scraped off with a micromanipulator and placed in a proteinase-K solution. DNA was extracted and amplified by the polymerase chain reaction (PCR) technique. Analysis of immunoglobulin JH gene rearrangement showed a distinct monoclonal band. In a second phase, using the same procedure in the same specimen, mantle zone cells around a germinal centre and single interfollicular B lymphocytes were isolated for PCR analysis of immunoglobulin JH gene rearrangement. In this population of cells, no clonality could be detected. This new technique allows the selective elimination of undesired cells and tissue from cutaneous neoplasms. By destruction of unwanted tissues with laser-beam energy a contamination-free sample is obtained. Analysis of isolated cells in our case demonstrated a clonal rearrangement derived from germinal centre cells and not from other B lymphocytes in the specimen, confirming the diagnosis of cutaneous follicle centre lymphoma. The method described has exciting implications for dermatology and dermatopathology, allowing precise correlation of morphological features with findings by molecular genetics.
Cell Separation↗
Primary B-cell lymphomas of the skin.
Primary B-cell lymphomas of the skin are not as rare as is generally believed. They are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations over a period of at least six months when complete staging has been performed. The major subtypes are follicle center-cell lymphoma of the head and trunk, immunocytoma and large B-cell lymphoma of the leg (EORTC classification 1996). Also of interest is the recently recognized marginal-zone B-cell lymphoma. Primary B-cell lymphomas of the skin differ significantly from nodal lymphomas. Awareness of their special clinical behavior should prevent unnecessarily aggressive treatment.
Humans↗
Kinetic evidence for the existence of a rate-limiting step in the reaction of ferric hemoproteins with anionic ligands.
The kinetics of azide and fluroide binding to various monomeric and tetrameric ferric hemoproteins (sperm whale Mb, isolated alpha and beta chains of human Hb reacted with p-chloromercuribenzoate, dromeday, ox and human Hb) has been investigated (at pH 6.5 and 20 degrees C over a large range (20 microM to 2 M) of ligand concentration. It has been observed that the pseuo-first-order rate constant for azide binding to the hemoproteins investigated does not increase linearly with ligand concentration, but tends to level off toward an asymptomatic concentration-independent value typical for each hemoprotein. This behavior, which has been detected only by an investigation covering an unusually large range of ligand concentrations appears to be independent of the ionic strength, and it underlies the existence of a rate-limiting step in the dynamic pathway of azide binding to ferric hemoproteins, which is detectable whenever the observed pseudo- first-order rate constant becomes faster than a given value characteristic of the specific hemoprotein. Such a behavior is not observed in the case of fluroide binding probably because the pesudo- first-order rate constant for this ligand is much slower and never attains a value faster than that of the rate-limiting step. In general terms, this feature should involve a conformational equilibrium between at least two forms (possibly related to the interaction of H2O with distal histidine and its exchange with the bulk solvent) which modulates the access of the anionic ligand into the heme pocket and its reaction with the ferric iron.
Animals↗
[Cutaneous large cell anaplastic Ki-1 (CD 30) positive T-cell lymphoma].
A 72-year-old female patient presented with a large ulceration on the lower half of her right abdomen. Cutaneous anaplastic large-cell lymphoma was diagnosed based upon histopathological and immunohistochemical features. There were no signs of extracutaneous involvement by the lymphoma. Complete remission was achieved by local electron beam radiation, followed by chemotherapy.
Abdominal Neoplasms↗
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↗