Unusual clinical manifestation and challenging serological interpretation of syphilis: insights from a case report.

BACKGROUND: The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus (HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. CASE PRESENTATION: In 2020, a 52-year old HIV-positive bisexual male patient was admitted to our department with a 4-month history of moderately itchy cutaneous lesions localized at his neck, trunk and arms. In 2013, the patient presented with a classic syphilitic roseola of the trunk and a secondary syphilis was diagnosed, with increased levels of rapid plasma reagin (RPR), Treponema pallidum hemagglutination assay (TPHA), anti-Treponema pallidum IgM and IgG Index. A second episode occurred in 2018, as a primary syphilis with multiple ulcerative lesions of the penis, and increased levels of RPR, IgG and IgM. In 2019, a further episode of secondary syphilis was treated with Doxycycline. In 2020, erythematous and papular lesions with vesicular components and urticarial erythema multiforme (EM)-like lesions were present at the neck, trunk and arms. Serological tests and Nucleic Acid Amplification Test (NAAT) for Treponema Pallidum were performed, as well as a cutaneous biopsy with histological and immunohistochemical evaluation of one lesion. NAAT was negative for T. pallidum. Serological test results were discordant with a new syphilis infection, showing only increased levels of RPR and anti-Treponema IgG. The cutaneous biopsy revealed a non specific histological pattern, while the immunohistochemical evaluation with anti-spirochetal antibodies was mandatory for the diagnosis of recent syphilis, showing clusters of rod-shaped elements, some of which with spiral form, focally present at the epidermis and adnexal structures. CONCLUSIONS: Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.

Adenocarcinoma of the cervix associated with a neuroendocrine small cell carcinoma of the cervix in the spectrum of Muir-Torre syndrome.

Muir-Torre syndrome (MTS) is an autosomal genodermatosis that is diagnosed by the presence of at least one sebaceous gland tumor and at least one visceral malignancy. The most frequent visceral malignancies reported in literature are low-grade colon-rectal and genitourinary cancers, with prolonged survival. The authors report the case of a 52-year-old female, with a positive familial history for MTS, who developed a cutaneous sebaceous carcinoma, a synchronous colon-rectal adenocarcinoma, and a metachronous endocervical adenocarcinoma associated with a neuroendocrine small cell carcinoma of the cervix (SCNC), with lymph node metastasis. The rare occurrence in literature of the cervical SCNC and the rarest occurrence of a neuroendocrine carcinoma in the context of a MTS deviate from the usual and low-grade types of cancers normally described with MTS. It should be always appropriate to assess any symptoms that might reveal an underlying malignancy, although not within the spectrum of neoplasms most associated with this rare syndrome.

Meat quality of buffalo young bulls fed faba bean as protein source.

Sixteen Italian Mediterranean Buffalo young bulls were divided into two groups fed isoprotein and isoenergy diets and only differing for protein source of concentrate: faba bean (FB) vs soybean (SB). Animals were slaughtered at 350 kg BW. Meat from FB group showed significantly lower fat, protein, cholesterol and saturated fatty acids than SB group. Significant differences were also found between the three muscles analysed [Longissimus thoracis (LT), Semitendinosus (ST) and Iliopsoas plus Psoas minor (IP)]. ST showed the most favourable fatty acids profile: lower SFA, higher PUFA, MUFA, ω-3, ω-6, CLA and, consequently, lower values for both atherogenic and thrombogenic indexes. Results showed that faba bean can be used as a protein source alternative to soybean in the diet of young buffalo bulls for the production of high quality meat.

Visceral leishmaniasis revealed by a squamous cell carcinoma in an HIV-1 infected patient.

We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.

Lichen sclerosus and the risk of malignant progression: a case series of 159 patients.

AIM AND METHODS: We analyzed 159 stored specimens of Lichen Sclerosus (LS) collected in the period 1999-2011 from 159 patients, in order to evaluate the histological patterns, clinical outcomes and possible associations with malignancies. The histopathologic analysis revealed 145 cases (males and females) with LS alone, 7 in whom penile LS was associated with spinocellular carcinoma (SCC), and 7 in whom LS was associated with a pseudocarcinomatous-hyperplasia (PCH). Extragenital LS was found in 20% (17/85) of the males and 78% (58/74) of the females. In the cases of SCC, immunohistochemical analyses was performed. RESULTS AND CONCLUSION: The results showed very low positivity to p16INK4A and Ki-67; biomolecular PCR was positive in only two cases, and in both cases the non-oncogenic genotype HPV 100 was detected. No important additional risk factors for malignancies were found (e.g., hormones, infections, other autoimmune diseases).

Preoperative advantages of HF sonography of pilonidal sinus.

AIM AND METHODS: Pilonidal sinus is a not infrequent disease, probably due to a disontogenetic origin. Histologically, there is a pseudocystic formation in the subcutaneous adipose tissue, containing some hair bulbs. It usually presents a recurring inflammatory course. The pathologic formation does not normally have thick wall, being made up of thin epidermal epithelium, without internal vascularisation and with frequent subcutaneous fistulae. Even though the clinical diagnosis is rather easy, surgery may prove, on the contrary, a demanding task, with a high incidence of recurrence and complications. An adequate knowledge of the condition and its development, with a precise definition of the margins of the lesions, may simplify the surgery, reducing the chance of recurrence or complications. The use of echography in the diagnosis of this disease, in our cohort of 72 patients, has always provided valuable information. In particular, 13 and 18 MHz linear probes and 20 MHz mechanical array have been used, and the latter in particular for the evaluation of fistolous cavities/passageways under the skin. Results. In all our cases, echography has demonstrated pseudocystic formations, without real walls, with fairly high levels of internal echoes, compared to the hair follicles, or, more rarely, true macrocalcifications with one or more cavities/passageways near the skin, without internal vascularisation, according to the histological findings. Echographic data are rapidly obtained, and can prove useful for surgeons for a a better management of patients. Conclusion. We consider diagnostic echography, using high frequency probes, useful for the anatomical definition of this disease, as well as to enable better surgical management.

Pilot study on reflectance confocal microscopy imaging of lichen planus: a real-time, non-invasive aid for clinical diagnosis.

BACKGROUND: Lichen planus (LP) represents a relatively common skin inflammatory entity included in the major group of interface dermatitis. In recent years, reflectance confocal microscopy has demonstrated to be a valuable tool for the 'in vivo' characterization of various skin diseases with cellular level resolution. No data are currently available that uses reflectance confocal microscopy to study LP. OBSERVATIONS: In this study, we have investigated the clinical and confocal features of five cases of histopathologically proven LP, and we have correlated the observed features with histopathological findings. The most characteristic criterion was the presence of interface dermatitis. Papillary rims, usually visible in normal skin, were obscured by the presence of a diffuse inflammatory cells infiltrate, arranged in sheet-like structures that surrounded the junction almost completely. There was an almost total obliteration of the ring-like structures around DP, which appeared non-edged and non-rimmed. Granular cells appeared as very large, polygonal structures, with an evident grainy cytoplasm, with the transition between spinous and granular cells being clearly recognizable, and this feature corresponded to hypergranulosis in histology. The presence of inflammatory cells at the level of the epidermis was seen as round-to-polygonal bright structures in the context of a variable degree of epidermal disarray and spongiosis. Melanophages in dermis were visible as brightly refractile, plump, oval to stellate-shaped cells. Prominent round or linear dark canalicular structures corresponded to dilated blood vessels in the superficial dermis on histopathology and appeared horizontally oriented in confocal sections. CONCLUSIONS: Reflectance confocal microscopy may represent a real-time, non-invasive aid to clinical diagnosis of LP. However, it might be difficult to distinguish between different subtypes of interface dermatitis. Further research, including larger case series, will better define a possible differential diagnosis of these diseases using confocal microscopy.

[The surgical treatment of thin melanoma]. / La chirurgia del cosiddetto melanoma sottile.

Examination of more than 700 cutaneous melanoma cases, the authors have identified 19 so-called thin melanomas, which have evolved in the long time in metastases. Two tumor distinctive features, vascularization and regression, correlated between them, seem to be particularly important in outlining the future tumor behavior, and so these two parameters must be analysed and included in the histological report. In these cases it is undoubted the need to make a strict surveillance protocol, also more than 10 years. According to our opinion, surgical treatment can immediately provides, in selected cases, the use of sentinel lymph node technique or the integration with other therapies (immuno-treatment).

Morpheaform extra-ocular sebaceous carcinoma.

BACKGROUND: Sebaceous carcinoma is an unusual, aggressive, malignant tumor derived from the epithelium of sebaceous glands. It may arise in ocular or extra-ocular sites and is often evident as an ulcerated or non-ulcerated cystic nodule measuring up to 8 cm in diameter. A significant number of extra-ocular sebaceous carcinomas have been associated with metastases and high mortality rate. METHODS AND RESULTS: We reviewed the literature in the context of our report of a 68-year-old woman who had a morpheaform plaque of the upper lip of 15 years duration, extending into the left naso-genal groove, which histologically also showed marked stromal fibrosis. Three years after excision, there were no signs of recurrence or metastases. CONCLUSIONS: This patient is unusual in clinical and histologic pattern, as a morpheaform appearance has only been described previously in only one sebaceous carcinoma. In addition, no metastatic disease 15 years after tumor onset is a fortunate and remarkable feature.

Microinvasive squamous cell carcinoma arising on lichen sclerosus of the penis.

The case of a 70-year-old white man with a 10-year history of penile lichen sclerosus (LS) who developed microinvasive squamous cell carcinoma on LS is described. A high incidence of penile cancer arising on genital LS has recently been observed. The authors stress the importance of an adequate diagnosis and long-term follow-up in patients with penile LS because of the malignant potential of the disease.

Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis.

Lipoprotein (a) [Lp(a)] has been associated with both anti-fibrinolytic and atherogenic effects. However, no direct link currently exists between this atherogenic lipoprotein and intravascular coagulation. The current study examined the binding and functional effects of Lp(a), its lipoprotein constituents, apoliprotein (a) [apo(a)] and low-density lipoprotein (LDL), and lysine-plasminogen (L-PLG), which shares significant homology with apo(a), on tissue factor pathway inhibitor (TFPI), a major regulator of tissue factor-mediated coagulation. Results indicate that Lp(a), apo(a), and PLG but not LDL bound recombinant TFPI (rTFPI) in vitro and that apo(a) bound to a region spanning the last 37 amino acid residues of the c-terminus of TFPI. The apparent binding affinity for TFPI was much higher for Lp(a) (KD approximately 150 nM) compared to PLG (KD approximately 800 nM) and nanomolar concentrations of apo(a) (500 nM) inhibited PLG binding to TFPI. Lp(a) also inhibited in a concentration-dependent manner rTFPI activity and endothelial cell surface TFPI activity in vitro, whereas PLG had no such effect. Moreover physiologic concentrations of PLG (2 microM) had no effect on the concentration-dependent inhibition of TFPI activity induced by Lp(a). In human atherosclerotic plaque, apo(a) and TFPI immunostaining were shown to coexist in smooth muscle cell-rich areas of the intima. These data suggest a novel mechanism whereby Lp(a) through its apo(a) moiety may promote thrombosis by binding and inactivating TFPI.

Plasmin proteolysis of endothelial cell and vessel wall associated tissue factor pathway inhibitor.

Plasmin is an important protease that mediates clot fibrinolysis and vessel wall extracellular matrix proteolysis. Recently, in vitro studies have suggested that plasmin can cleave and inactivate recombinant TFPI, a major inhibitor of TF-mediated coagulation. We hypothesized that such an interaction may occur in vascular cells expressing TFPI, or in the vessel wall, with implications for thrombolysis. In a series of experiments, we examined the effects of plasmin on cell surface and extracellular matrix (ECM) associated TFPI in endothelial cells (EC) in culture and on EC and smooth muscle cells (SMC) in the vessel wall. Plasmin (0.2 microM) decreased cell surface and matrix associated TFPI activity in cultured endothelial cells by 77 +/- 5% and 69 +/- 6% respectively (p < 0.01). Plasminogen, the proenzyme form of plasmin had no such effect on cell surface TFPI or matrix TFPI. Cell surface TFPI antigen measured by fluorescence activated cell sorter (FACS) was also significantly reduced by plasmin. Proteolysis of conditioned medium TFPI was suggested by loss of a approximately 45kD TFPI on Western Blot analysis following plasmin treatment. Plasmin also proteolysed a approximately 45kD TFPI protein in the intact ECM of EC, an effect which was inhibited by preincubation with aprotinin, a plasmin inhibitor. Incubation of similar concentrations of plasmin, with homogenates of normal vessel decreased a approximately 45kD TFPI immunoreactive band on Western blot analysis. Plasmin also decreased surface TFPI activity on frozen sections of normal vessel as measured by an amidolytic assay. Finally, plasmin treatment of atherosclerotic plaque sections caused complete removal of TFPI immunoreactivity associated with luminal EC and intimal SMC, when compared to control treated plaque (n = 3). Together these data suggest that plasmin proteolyses the majority of EC-associated (surface and matrix) TFPI and may remove TFPI from the luminal surface and intima of the vessel wall. TFPI proteolysis in cultured EC was associated with significant reduction in TFPI anticoagulant activity. These data provide evidence that plasmin degradation of TFPI occurs in vascular cells and in the vessel wall and may have implications for re-thrombosis following thrombolysis in vivo.

Evidence of patent ductus arteriosus and right-to-left shunt by finger pulse oxymetry and Doppler signals of agitated saline in abdominal aorta.

The diagnosis of patent ductus arteriosus (PDA) with right-to-left shunt in the adult by using transthoracic echocardiography (TTE) is difficult because of limited windows. We report a case of a 23-year-old woman who was referred for treatment of primary pulmonary hypertension but was found to have a PDA with a right-to-left shunt. On examination she had asymmetric hypoxia of the upper extremities on finger pulse oxymetry. Transthoracic echocardiography revealed a large right atrium and no atrial or ventricular septal wall defects. The diagnosis of PDA with Eisenmenger's syndrome was made after evidence of a right-to-left shunt was confirmed by Doppler signals of intravenous agitated saline in the abdominal aorta. This case illustrates the utility of Doppler signals from agitated saline in the abdominal aorta and finger pulse oxymetry, in addition to physical examination, in the diagnosis of PDA with right-to-left shunt.

Identification of fibrillins as a major component of coronary atherosclerotic plaques.

Fibrillins are two distinct 350 kD RGD-containing glycoproteins found in microfibrils in the extracellular matrix. Fibrillin-containing microfibrils are required for elastic fiber formation and serve as an anchor for protein binding via ß1 and/or αvß3 receptors. Fibrillin-1 is causally linked to Marfan's syndrome, which is in part characterized by disruption of the aortic media. Fibrillin-2 is causally linked to congenital contractural arachnodactyly, which is rarely characterized by cardiovascular symptoms. We hypothesized that fibrillins might be present in coronary atherosclerotic plaques and contribute to plaque stability. To test this, we examined the expression of fibrillins-1 and -2 in human coronary arteries and coronary atherectomies. Positive staining for fibrillin-1 and fibrillin-2 proteins was observed by immunochemistry in 95% of the specimens. Fibrillin-1 was localized to the plaque, adventitia, and endothelial cells. Fibrillin-2 stained diffusely in the adventitia and focally in the plaque. Neither fibrillin was abundant in the media. Substantial differences between the amount and localization of histologically stained elastic fibers and fibrillin immunohistochemical staining were noted. By in situ hybridization, fibrillin-1 mRNA was localized to smooth muscle cells, endothelial cells, and fibroblasts. In spite of the presence of fibrillin-2 antigen by immunohistochemistry, fibrillin-2 mRNA was not detected by in situ hybridization. These data implicate fibrillins as important components of the atherosclerotic plaque. Fibrillins may contribute to plaque stability and act as binding sites for other macromolecules within the atherosclerotic lesion.