Histopathological study of perilesional skin in patients diagnosed with nonmelanoma skin cancer.

BACKGROUND: Epidemiological and clinical data suggest that actinic damage to the skin is an important predictor of skin carcinogenesis. AIM: To investigate the association of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with sun-damage alterations seen by histopathology. METHOD: In the current prospective study, perilesional skin of SCC or BCC lesions was evaluated for presence of alterations associated with chronic photodamage. Presence of scarring, perineural/perivascular invasion, haemorrhage/haemorrhagic crust, ulceration/erosion and margin involvement were also assessed. RESULT: Of 6038 included lesions, 4523 (74.9%) were BCCs and 1515 (25.1%) were SCCs. Presence of actinic damage was five times more frequent in SCC than in BCC (OR = 5.29, 95% CI 4.44-6.00, P < 0.001), and diagnosis of SCC was twice as common in photo-exposed than nonphoto-exposed body sites (OR = 2.34, 95% CI 2.03-2.70, P < 0.001). There were twofold higher odds for actinic damage in SCC compared with Bowen disease (OR = 2.015, 95% CI 1.55-2.61, P < 0.001). Assessing the different BCC histological subtypes, we found that nodular BCC had at least twofold higher odds (OR = 2.63, 95% CI 2.09-3.32), infiltrative BCC had 48% higher odds (OR = 1.487, 95% CI 1.18-1.87) and basosquamous BCC had fourfold higher odds (OR = 4.10, 95% CI 3.01-5.57) of having actinic damage compared with superficial BCC. CONCLUSIONS: Histological verification of ultraviolet-associated alterations in the perilesional skin in patients with NMSC in our study confirms the aetiopathogenic link between sun exposure and epithelial carcinogenesis on a histopathological basis. This correlation was stronger for SCCs than for BCCs.

Surgical treatment of basal cell carcinoma and squamous cell carcinoma.

Non melanoma skin cancers (NMSC) are the most common human neoplasms, encompassing basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but also cutaneous lymphomas, adnexal tumors, merckel cell carcinoma and other rare tumors. The incidence of BCC and SCC varies significantly among different populations, and the overall incidence of both tumors has increased over the last decades. Although generally associated with a favorable prognosis, recent evidence suggests that the mortality rates of SCC might have been underestimated up-to-date.1 According to Medicare data, NMSC is the fifth most expensive cancer for health care systems. This increased economic burden is not associated with the cost of treating an individual patient, but with the large number of affected patients and the recurrence rates.2 Therefore, the adequate management of the primary tumor with a complete excision becomes a priority not only for the patient but also for the public health systems. Multiple treatment modalities are currently usedin clinicalpractice for the treatment of NMSC. While surgical excision (SE) remains the gold standard of care, non-surgical techniques have gained appreciation due to lower morbidity and better cosmetic results. The optimal management of treatment includes a complete tumor clearance, preservation of the normal tissue function, and the best possible cosmetic outcome.3 Surgery with a predefined excision margin is the treatment of choice for most NMSCs, with Mohs micrographic surgery being recommended for tumors considered to be at a higher recurrence risk or those developing on cosmetically sensitive areas.4, 5 Therefore, the surgical approach of a NMSC consists with three different and equally important steps. First the preoperative clinical assessment of the tumor margins, which can be facilitated by the use of dermoscopy. Second, the definition of the surgical margins depending on the tumor subtype and its biological behavior. Finally, the surgical procedure must be designed based on the anatomic site and the patient's charachteristics. This preoperative assessment requires specific skills and might be performed by a physician, the dermatosurgeon, two collaborating specialists, namely a dermatologist and a surgeon.

Matter of margins.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer, it represents a significant economic burden to health services because of a large volume of affected patients. Surgical excision with histological assessment of the surgical margins is widely considered as the mainstay of BCC treatment. Incomplete removal, in fact, should be considered a poor prognostic indicator, as incomplete removal of lesions is at risk of local recurrence. Actually, dermatological surgeries are carried out by a variety of different types of practitioners, such as plastic surgeons, maxillofacial surgeons, otorhinolaryngologists, ophthalmologists and finally dermatologists. Incomplete removal of the tumour ranges from 6.3% to 25%, depending on the improper intra-operative evaluation of the extent of the tumour. It depends on the clinical knowledge derived from both training and daily experience. In this sense, the majority of the largest studies derive from plastic surgeons, while dermatologists have small case series, albeit with a higher therapeutic efficacy in terms of complete surgical excision. OBJECTIVES: We conducted a retrospective analysis of the surgical activity, more specifically we evaluated both our therapeutic accuracy and analyzed the prognostic factors related to incomplete excisions. METHODS: A retrospective review of all BCC removals was performed. A total of 4523 BCC removals were included; other neoplasm, benign lesions and biopsies were also excluded. Each BCC's size diameter, localization, histology and histological presence of complicating factors was assessed, then the percentage of the incomplete removal was calculated. RESULTS: Incomplete resections occurred in 225 (4.97%) BCCs of the cases. Thirteen areas were categorized into in three different levels that rank the risk of incomplete removals. Sub-analysis indicates that just over a third had no complicating factors with the lateral/deep margins. The most frequent complicating factor is ulceration (22.9%), while vascular invasion or seborrheic keratoses were not found. Actinic keratoses, scabs and scars held the most responsibility for the involvement of the lateral margins, while perineural invasion is the main factor leading to deep margin involvement. Finally, a different trend for the involvement of lateral or deep margins according different histological sub-types was highlighted; lateral involvement is more frequent for the infiltrative/morpheic type, while the deep margin is more involved in the nodular type.

Recurrent migratory angioedema as cutaneous manifestation in a familiar case of TRAPS: dramatic response to Anakinra.

BACKGROUND: Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) is a hereditary autoinflammatory syndrome characterized by recurrent episodes of fever and localized inflammation. Clinical presentation can be very variable in terms of duration of fever attacks, periodicity, and accompanying manifestations. One of the most characteristic symptoms is the occurrence of migrating skin rash with myalgia that is sustained by monocytic inflammation. OBSERVATIONS: We herein present the case of a family suffering from TRAPS who had been misdiagnosed for a long period of time and whose main symptom was migrating angioedema. Skin biopsy from one of the patients documented a monocytic panniculitis. All the living patients responded dramatically to anakinra treatment. CONCLUSIONS: The classic symptom of migratory angioedema with myalgia in TRAPS can be produced by monocytic panniculitis.This manifestation is so characteristic of TRAPS that its occurrence, even in the absence of other manifestations, should prompt genetic analysis. Our patient's condition responded promptly to anakinra treatment.

Borrelia burgdorferi-associated primary cutaneous marginal-zone B-cell lymphoma: a case report.

An association between Borrelia burgdorferi with primary cutaneous B-cell lymphoma (PCBCL) has long been suspected but just recently, thanks to a polymerase chain reaction technique, it had been possible to demonstrate B. burgdorferi-specific DNA in skin lesions of patients with different PCBCL subtypes. Locating cases of PCBCL that are related to B. burgdorferi infection could be really important for therapeutic implications; in fact, there are several reports of PCBCL responding to antibiotic therapy against B. burgdorferi. We report a case of B. burgdorferi-associated primary cutaneous marginal-zone B-cell lymphoma that, after specific antimicrobial therapy, did not show any clinical regression. We can conclude that additional studies are necessary in order to establish the use of antimicrobial therapy in B. burgdorferi-associated PCBCL.

An imported case of adult T cell leukemia in a HTLV-I-infected patient in Italy.

In this study we report the case of an acute form of ATL in a HTLV-I-infected Nigeria-born 27-year-old female prostitute living in Italy from February, 2001. The presence of HTLV-I infection was demonstrated by the detection of serum antibody to HTLV-I by immunoenzymatic assay and western blot analysis. In addition, the presence of HTLV-I proviral DNA was confirmed by a hemi-nested PCR in a sample of peripheral blood mononuclear cells. From an epidemiological point of view, it is important to report new cases of imported ATL, as it may explain the otherwise untraceable origin of some rare and apparently autochthonous cases of ATL in non-endemic areas.

Human T cell leukemia virus type II increases telomerase activity in uninfected CD34+ hematopoietic progenitor cells.

The aging process of long-term self-renewing hematopoietic stem/progenitor cells is not yet completely understood and recent studies on antiapoptotic cell pathways have demonstrated a close linkage between telomerase activation and Bcl-2 deregulation in human cancer cells. The present work shows that human T cell leukemia virus type II (HTLV-II) Mo virions that have originated from the T cell line (C344), but not from the B cell line (BJAB), are critically involved in mediating survival and growth effects on hematopoietic precursors (represented by both the TF-1 CD34+ cell line and by peripheral blood-derived CD34+ cells) through the maintenance or enhancement of telomerase activity and the induction of bcl-2 expression. In addition, using an interleukin-3-dependent TF-1 cell line, it was demonstrated that IL-3 deprivation was sufficient to influence the levels of telomerase activity and Bcl-2 expression in CD34+ cells. Taken together, these findings suggest that, in appropriate conditions, extended hematopoietic progenitor cell survival and proliferation following HTLV-II exposure depends on a synergistic interaction between up-regulation of Bcl-2 and activation of telomerase activity.

Human T-cell leukemia virus type II directly acts on CD34+ hematopoietic precursors by increasing their survival potential. envelope-associated HLA class II molecules reverse this effect.

The role of human T-cell leukemia virus type II (HTLV-II) in human lymphoproliferative and hematopoietic abnormalities in which the retrovirus can be isolated is still elusive. Here we show that the C344 T-cell-derived lymphotropic HTLV-II type IIa Mo strain acts directly on CD34+ hematopoietic precursors by rescuing them from apoptosis induced by interleukin-3 (IL-3) deprivation. This effect is viral strain-specific, as it is not observed with the B-lymphotropic HTLV-II type IIb Gu strain, it does not require infection of the hematopoietic precursors, and, interestingly, it is strongly dependent on the infected cellular host from which the virus was derived. Indeed, growth adaptation of the Mo strain to the permissive B-cell line, BJAB, renders the virus no longer capable of mediating the antiapoptotic effect. However, pretreatment of the BJAB-adapted Mo strain with antibodies specific for HLA class II, but not class I, histocompatibility antigens restores the antiapoptotic potential of the virus. These results constitute the first evidence that HTLV-II retrovirus can directly influence the homeostasis of human progenitors, without infecting them, and that this crucial activity is strongly inhibited by the presence of host-derived envelope-associated HLA class II antigens.

The lack of susceptibility to HIV-1 infection in human hematopoietic progenitor TF-1 cell line correlates with the absence of LFA-1 (CD11a) surface adhesion molecule.

Although substantially unsusceptible to HIV-1 infection, human hematopoietic progenitors (CD34+ cells) express significant amounts of gp120-binding CD4 molecules. As some experimental evidence suggests the need for one or more putative cellular accessory factor(s) for efficient CD4-mediate HIV-1 infection, we analyzed the presence and distribution of various adhesion molecules on the surface of two HIV-1-susceptible cell lines (H9 and A3.01) and one HIV-1-unsusceptible, CD4-positive, human hematopoietic progenitor cell line (TF-1). The only difference observed concerned the LFA-1 CD11a protein that has already been shown to be necessary for cell fusion in HIV-1-infected T4 lymphocytes. CD11a was present in a high percentage of HIV-1-susceptible cells and absent in HIV-1-unsusceptible TF-1 cells. A significant increase in HIV-1 replication was obtained in CD11a-enriched H9 cells in comparison with an almost completely CD11a-deprived H9 cell population. The lack of susceptibility to HIV-1 infection in human CD34+ cells may depend on various factors. Nevertheless, the lack of CD11a in a CD34+, CD4+ human hematopoietic progenitor cell line suggests that this molecule may be implicated in the susceptibility to HIV-1 infection.

Human T-lymphotropic virus type I (HTLV-I) provirus-related DNA sequences in peripheral blood mononuclear cells of a patient, in the absence of a definite serological positivity.

The true extent of human T-lymphotropic virus type I and II (HTLV-I/II) infection in European countries and its pathogenetic potential are still unknown. To find out more about HTLV-I/II incidence in our area we studied a group of 160 outpatients attending a sexually transmitted disease clinic over a six-month period. All patients were screened for the presence of specific antibody by means of enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB) analysis, using commercially available reagents. A surprisingly high percentage of patients showed an antibody reactivity to HTLV-I/II antigens by ELISA (9.3%) and IB (6.8%), although none of the samples satisfied the internationally accepted criteria of serological positivity. All subjects, irrespective of doubtful and inconclusive serological results, were further analyzed for the presence of proviral DNA in peripheral blood mononuclear cells by polymerase chain reaction using different pairs of primers and probes. A clear cut positive result for the presence of HTLV-I provirus-related DNA sequences was obtained in peripheral blood mononuclear cells of only one patient, a 26 years old female presenting genital condylomatosis, with no history of blood transfusion and/or intravenous drug abuse. Her serum showed a borderline result at ELISA and an IB reactivity only against p21. These data are open to various possible interpretations and, among others, may represent a hint for the presence of divergent antigenic variants of HTLV-I in the geographical area investigated.

Uninfected haematopoietic progenitor (CD34+) cells purified from the bone marrow of AIDS patients are committed to apoptotic cell death in culture.

OBJECTIVE: To determine the mechanism underlying the poor growth in vitro of haematopoietic progenitor cells isolated from HIV-1-infected patients. METHOD: Apoptotic death in liquid culture of bone-marrow CD34+ cells obtained from 11 HIV-1-seropositive patients and 18 HIV-1-seronegative donors was quantitatively monitored by a flow cytometry procedure. RESULTS: No significant differences in the percentage of apoptotic cells were noted between the two groups immediately after purification. When CD34+ cells were placed in liquid cultures supplemented with 2 ng/ml interleukin-3, the number of apoptotic cells progressively and significantly (P < 0.05) increased in all HIV-1-seropositive patients, while it remained constant in HIV-1-seronegative individuals. Although all HIV-1-seropositive patients showed signs of active viral replication in the bone-marrow micro-environment, progenitor CD34+ cells did not show the presence of active and/or latent HIV-1 infection. CONCLUSION: Our data demonstrate that CD34+ cells isolated from AIDS patients with active HIV-1 replication in bone-marrow accessory cells are committed to apoptotic death without being directly affected by productive infection.

The impaired number of circulating granulocyte/macrophage progenitors (CFU-GM) in human immunodeficiency virus-type 1 infected subjects correlates with an active HIV-1 replication.

In this paper we investigated the role played by human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of peripheral blood (PB) cytopenias of AIDS patients. The in vitro growth of PB granulocyte/macrophage progenitors (CFU-GM) was investigated in 45 HIV-1 seropositive (+) individuals at different stages of the disease. The number of circulating CFU-GM was significantly (p < 0.01) lower in AIDS patients (stages WR V-VI) than in HIV-1(+) asymptomatic individuals (stages WR I-II). Moreover, the presence of gag p 24 in the plasma and/or viral isolation from PB mononuclear cells of HIV-1(+) individuals was inversely correlated (p < 0.01) with the number of circulating CFU-GM, irrespectively with the stage of the disease. Viral isolates obtained from one asymptomatic and four symptomatic HIV-1(+) individuals were tested on the in vitro growth of normal hematopoietic progenitor (CD34+) cells, purified from PB of healthy donors. All the different viral isolates showed a dose-dependent inhibition of CD34+ cells, in the absence of either productive or latent infection. This suppressive effect was completely reversed by preincubating the different viral isolates with a polyclonal anti-gp 120 antibody before adding to normal CD34+ cells. These findings suggest a direct involvement of active viral replication products in the progressive impairment of hematopoiesis, characteristic of HIV-1(+) individuals in spite of the lack of a productive or latent infection of CD34+ hematopoietic progenitors.