José Fernando Val-Bernal

Human herpesvirus-8 genes are expressed in pulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor).

The presence of human herpesvirus-8 DNA sequences, as well as an overexpression of human interleukin-6 and human cyclin D1 in myofibroblastic cells of inflammatory myofibroblastic tumor (inflammatory pseudotumor), has recently been reported. We describe the pattern of human herpesvirus-8 gene expression in five cases of pulmonary inflammatory myofibroblastic tumor. Reverse transcriptase–polymerase chain reaction (RT-PCR), with several positive and negative controls, was performed to detect mRNA of 11 open reading frames encoded by human herpesvirus-8 in lytic and latent stages of viral replicative cycle. We found molecular transcripts from ORF16, ORFK13, and ORF72 in the five cases and from ORFK2 in four of five neoplasms. The corresponding encoded proteins were human homologous oncoproteins (viral cyclin-D), inflammatory cytokines (viral IL-6), and inhibitors of apoptotic pathways (viral FLIP and viral Bcl-2), mostly expressed in a latent viral replicative stage. The rest of open reading frames examined included mainly lytic-associated genes and showed no expression. The spectrum of expressed viral genes is not the same as can be observed in Kaposis sarcoma or multicentric Castlemans disease, suggesting that human herpesvirus-8 plays a different role in the pathogenesis of its associated diseases. These differences may be related to either cell-specific or immunologic host factors.

Presence of human herpesvirus-8 DNA sequences and overexpression of human IL-6 and cyclin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor).

Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma cells, and lymphocytes. Cytokines are possibly involved in its pathogenesis. Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins. A combination of nested PCR with several negative controls and Southern blot methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally, strong expression was demonstrated by in situ hybridization in many tumoral nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for human IL-6 and cyclin D1. These cytokines probably have a paracrine action and may sustain myofibroblastic growth. HHV-8 could play an essential role in triggering IMT development by a local reactivation of viral lytic replication. The relationship between HHV-8 and immunosuppression status as the only associated cause for tumorigenesis should be revised.

A type-specific study of human papillomavirus prevalence in cervicovaginal samples in three different Spanish regions

Human papillomavirus (HPV) is the most frequent sexually transmitted viral infection. It is necessary to know HPV genotype distribution to identify how many women will be protected by HPV vaccines. During a period of 18 months, we have analyzed 2362 HPV positive reporting data from a secondary demand screening program in three regions in Spain (Cantabria, Leon and Burgos). The study has been conducted using polymerase chain reaction and tube array hybridization covering the 35 HPV genotypes described as affecting anogenital mucosa. There were no significant differences between the three regions according to genotype distribution. The most frequent were HPV16 (19.18%), HPV53 (11.26%) and HPV58 (7.66%). HPV18 was the source of 4.02% of infections. High‐risk HPVs were found in 1863/2362 cases. HPV16 was present in 24.3% of high‐risk infections and HPV18 was found in 5.1%. Uncommon genotypes (<5% of the total prevalence each) were found in 17,9% of the total high‐risk infections (334/1863). Multiple infections were diagnosed in 22% of the cases. The HPV genotype distribution is different from previously published data when multiple types are included in the screening. Both HPV16/18 account for 30% of high‐risk infections in a clinical setting in Spain. The presence of multiple genotypes is very common among the population.

Subcutaneous phaeohyphomycosis caused by Exophiala oligosperma in a renal transplant recipient.

horns in the present report probably originated from longstanding verruca vulgaris lesions. It had been widely accepted that the horn arising from an exaggerated verruca vulgaris seldom reaches a height of 0Æ5 cm, but the horns in this case were exceptionally large, with the longest one reaching 21 cm, possibly indicating very special individual features. Verrucae vulgaris (skin warts) are kinds of benign proliferating lesions in epithelia, often on hands, and are usually caused by HPV infection. The present case contained intact HPV-2a genome sequences, which may present in episomal form. Whole genome alignment analyses of this isolate revealed very high homology with the HPV-2a prototype. Although several mutations have been identified in various regions, e.g. in E1, E7 and the long control region (LCR), even a nucleotide exchange in the potential E2 binding site in the LCR, it is hard simply to ascribe the presence of multiple horns to virus infection, as none of our patient’s family members or close contacts appeared to have a similar disorder during a period exceeding 30 years. Although it has been reported that HPV-2-related warts respond only modestly to treatment, as they persisted in approximately 50% of all patients for more than 6 additional months, the patient infected with HPV-2a in this study was successfully cured with a combined therapeutic protocol of systemic administration of tretinoin (acitretin) and interferon alfa-2b, and local irradiation with X-rays or electron beams. No recurrence of warts on the extremities or trunk has been observed. Radiation may directly suppress active epidermal proliferation. Tretinoin inhibits hyperkeratosis of epidermis, induces growth arrest of actively proliferating epidermal cells and increases the sensitivity of HPV-infected cells to radiation. Although the mechanism of appearance of hundreds of horns in this case still remains unknown, the combined use of antiviral agents and physical and chemical inhibitors of epithelial proliferation seemed to be effective in removing the infected lesions and in preventing recurrence.

Nuclear morphometry in prognosis of renal adenocarcinoma

Nuclear morphometry was carried out on 95 parenchymatous adenocarcinomas of the kidney treated by radical nephrectomy and hilar lymphadenectomy and followed up for at least five years. The study assessed nuclear area, nuclear perimeter, major diameter, nucleolar area, nuclear shape factor, and nuclear size. There was a significant statistical correlation between survival and the morphometric parameters and between the parameters themselves except for nuclear shape factor. The multiple regression proved that nuclear area is the factor which shows the greatest statistical significance for prognosis. Taking a mean nuclear area of 35 microns 2 allowed two prognostic groups to be established regardless of stage, with those below the threshold having a good prognosis and those above it having a poor prognosis: 96.7 percent of patients with a good prognosis survived after five years (60 months) compared with 17.2 percent of those with a poor prognosis.

New-onset psoriasis following treatment with the interleukin-1 receptor antagonist anakinra

et al., 38 patients had HZ, followed later (days to years) by different localized disorders (including squamous cell carcinoma, basal cell carcinoma, leukaemia, granuloma annulare, Kaposi sarcoma and tinea). A few published case reports mention an LP eruption after healing of HZ lesions. In regard to LP, several variations of lesional arrangement occur, including linear and zosteriform manifestations. The dermatomal distribution seen in our patient strikingly differs from an orientation according to Blaschko’s lines, thereby – according to Happle – excluding the diagnosis of linear LP. Furthermore, serological analysis with an elevated VZV IgA concentration in serum supports the assumption of a postzoster LP and not a spontaneous LP in a zosteriform arrangement. Nevertheless, other linear and ⁄or zosteriform cutaneous disorders must be delineated, including lichen striatus, inflammatory linear verrucous epidermal naevus, naevus unius lateralis, porokeratosis (linear type), verruca plana and epidermodysplasia verruciformis. To summarize, our case of LP arranged in an unilateral dermatomal way may be best explained by an isotopic response following HZ sine herpete.

Metastasis from small cell carcinoma of the lung producing acute appendicitis

A case of acute gangrenous appendicitis with perforation caused by metastatie small cell carcinoma of the lung in a 65 year old man is reported. The manifestation of appendicitis occurred more than 4 years after the diagnosis of the bron‐chogenic carcinoma. With longer survival of patients with disseminated tumors it is probable that new manifestations of those malignancies will be discovered. Acute appendicitis due to metastasis from a distant neoplasm should be considered in the differential diagnosis of right lower abdominal pain in the oncology patient.

Cardiac papillary fibroelastoma: Retrospective clinicopathologic study of 17 tumors with resection at a single institution and literature review

Cardiac papillary fibroelastomas (PFEs), which are mainly found in the valves, are rare benign tumors that can cause embolism. Single-center surgical experience in the treatment of this tumor is uncommon. All patients surgically treated for this neoplasm at our institution from January 1995 to October 2012 (15 patients with 17 lesions) were queried for clinical and pathologic characteristics, and the literature was reviewed. The mean age of detection was 55.8±11.48 years. Twenty percent of the patients were male. The tumor was an incidental finding in 60%. Symptoms directly related to PFEs occurred in 40% of patients. The most common clinical presentation in symptomatic cases was embolism (40%), mostly transient ischemic attack or stroke. Cardiac valves were predominantly involved (76.5%); the most commonly valve affected was the aortic valve (29.4%), followed by the mitral valve (17.6%). Concurrent valvular disease was observed in 41.7% of patients. The mean size of tumors was 11.4±7.9mm (range 2-25mm). In 86.7% of the patients, the tumor was solitary. The mitral valve was the most common origin of tumor systemic embolism. Fronds core could be the end stage of hypermature elastic fibers, which grows in apposition to young fibers. Simple surgical excision or valvular reconstruction was accomplished in most patients (58.3%). PFE is usually small, appears singly, and can cause potentially serious complications. Symptomatic and left side tumors should undergo surgical excision with valve-spare surgery when possible. Surgical removal of PFE is safe, efficacious, and definitive.

Epstein-Barr virus-associated adenocarcinomas and squamous-cell lung carcinomas.

The association of Epstein–Barr virus with pulmonary neoplasms has been restricted to lymphoepithelioma-like carcinomas in Asian patients. We have selected 19 pulmonary adenocarcinomas and squamous-cell carcinomas from 1545 pulmonary neoplasms diagnosed from 1996 to 2007 in an occidental population. All of them showed a low-power appearance confusing between an epithelial and a lymphoid neoplasm, with a dense lymphocytic infiltrate intermingled with neoplastic cells giving an image akin to lymphoepithelial complexes. Five carcinomas presented typical features of Lymphoepithelioma-like lung carcinomas; but six cases could be classified as squamous-cell carcinomas and eight as adenocarcinomas. A semiquantitative polymerase chain reaction method, Early RNA genes 1 and 2 in situ hybridization as well as Latent membrane protein immunostaining for Epstein–Barr virus DNA, RNA and protein detection methods were used in every case. None of Lymphoepithelioma-like carcinomas showed positivity for Epstein–Barr virus in any used method. Otherwise four squamous-cell carcinomas and eight adenocarcinomas (12 cases) demonstrated viral sequences in polymerase chain reaction and/or in situ hybridization analysis in neoplastic cells. Moreover two adenocarcinomas also displayed human herpesvirus 6 DNA sequences coamplification in molecular analysis. Protein immunostaining was focally positive in only three cases. We performed the same analysis in 70 more cases of conventional pulmonary squamous-cell carcinomas and adenocarcinomas that gave negative results. In conclusion, a subset of pulmonary squamous-cell carcinomas and adenocarcinomas show Epstein–Barr DNA and/or RNA sequences in neoplastic cells. This finding expands the spectra of epithelial cell common tumours Epstein–Barr virus associated.

Primary lymphoplasmacytoid lymphoma of the trachea with immunoglobulin G paraprotein.

A primary tracheal lymphoma with immunoglobulin G (IgG)‐associated monoclonal serum paraprotein treated with surgery and chemotherapy is reported. As far as we know this is the first lymphoplasmacytoid lymphoma reported in the tracheobronchial tree and the first with a serum and tissue IgG monoclonal paraprotein. Differential diagnosis must be made essentially with extramedullary plasmacytoma and mucosa‐associated lymphoid tissue lymphoma. CD‐45RB strong positivity and the absence of lymphoepithelial lesions may help to differentiate lymphoplasmacytoid lymphoma from them. We expand the spectrum of lymphoid lesions with plasmacytoid features that can occur in the tracheobronchial tract.