SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence.

BACKGROUND: In the non-ETS fusion of prostate cancer (PCa) pathway, SPOP mutations emerge as a distinct oncogenic driver subclass. Both SPOP downregulation and mutation can lead to SPOP target stabilization promoting dysregulation of key regulatory pathways. CHD1 gene is commonly deleted in PCa. CHD1 loss significantly co-occurs with SPOP mutations, resulting in a PCa subclass with increased AR transcriptional activity and with a specific epigenetic pattern. METHODS: In this study, SPOP alterations at mutational and protein levels and CHD1 copy number alterations have been analyzed and correlated with ERG and PTEN protein expression and with the clinical pathological features of the patients. RESULTS: SPOP protein loss has been detected in 42.9% of the cases, and it has been strongly associated with PTEN protein loss (p < .001). CHD1 gene loss has been detected in 24.5% and SPOP mutations in 5.9% of the cases. Loss of CHD1 has been strongly associated with SPOP mutations (p = .003) and has shown a trend to be associated with ERG wt cancers (p = .08). The loss of SPOP protein (p = .01) and the combination of PTEN and SPOP protein loss (p = .002) were both statistically more common in grade group 5 cancers, with a prevalence of 60% and 37.5%, respectively. Furthermore, SPOP loss/PTEN loss and SPOP wt/PTEN loss phenotypes were strongly associated with extraprostatic perineural infiltration (p = .007). Strong CHD1 loss was associated with a shorter time to PSA recurrence in the univariate (p = .04), and showed a trend to be associated with the PSA recurrence risk in the multivariate analysis (p = .058). CONCLUSIONS: The results of the present study suggest that the loss of SPOP protein expression, either alone or in combination with loss of PTEN and, on the other hand, a marked loss of the CHD1 gene are very promising prognostic biomarkers in PCa.

SARS-CoV-2 identified by transmission electron microscopy in lymphoproliferative and ischaemic intestinal lesions of COVID-19 patients with acute abdominal pain: two case reports.

BACKGROUND: SARS-CoV-2 may produce intestinal symptoms that are generally mild, with a small percentage of patients developing more severe symptoms. The involvement of SARS-CoV-2 in the physiopathology of bowel damage is poorly known. Transmission electron microscopy (TEM) is a useful tool that provides an understanding of SARS-CoV-2 invasiveness, replication and dissemination in body cells but information outside the respiratory tract is very limited. We report two cases of severe intestinal complications (intestinal lymphoma and ischaemic colitis) in which the presence of SARS-CoV-2 in intestinal tissue was confirmed by TEM. These are the first two cases reported in the literature of persistence of SARS-CoV-2 demonstrated by TEM in intestinal tissue after COVID 19 recovery and SARS-CoV-2 nasopharyngeal clearance. CASE PRESENTATION: During the first pandemic peak (1st March-30th April 2020) 932 patients were admitted in Hospital Universitari Mútua Terrassa due to COVID-19, 41 (4.4%) required cross-sectional imaging techniques to assess severe abdominal pain and six of them (0.64%) required surgical resection. SARS-CoV-2 in bowel tissue was demonstrated by TEM in two of these patients. The first case presented as an ileocaecal inflammatory mass which turned to be a B-cell lymphoma. Viral particles were found in the cytoplasm of endothelial cells of damaged mucosa. In situ hybridization was negative in tumour cells, thus ruling out an oncogenic role for the virus. SARS-CoV-2 remained in intestinal tissue 6 months after nasopharyngeal clearance, suggesting latent infection. The second patient had a severe ischaemic colitis with perforation and SARS-CoV-2 was also identified in endothelial cells. CONCLUSIONS: Severe intestinal complications associated with COVID-19 are uncommon. SARS-CoV-2 was identified by TEM in two cases, suggesting a causal role in bowel damage.

SPOP and FOXA1 mutations are associated with PSA recurrence in ERG wt tumors, and SPOP downregulation with ERG-rearranged prostate cancer.

BACKGROUND: ERG fusion-related prostate cancer (PrCa) is the most prevalent oncogenic driver subclass. SPOP, FOXA1, and IDH1 mutations are other three main oncogenic driver subclasses in non-ETS-fusion PrCa. ERG protein levels seem to be increased in SPOP-mutated cases, and different studies reported that SPOP mutations and ERG fusions are mutually exclusive. The aim of this study has been to analyze the alterations in non-ETS-oncogenic drivers in PrCa. METHODS: SPOP, FOXA1, and IDH mutations were investigated by polymerase chain reaction (PCR) and Sanger direct sequencing. ERG, SPOP, and TMPRSS2-ERG messenger RNA expression was assessed by quantitative real-time PCR from complementary DNA, and the presence of the fusion was also analyzed by nonquantitative PCR. The clinical pathological features were retrieved from the charts of the 111 patients included in the study (MARBiobanc, Barcelona, Spain). RESULTS: Loss of SPOP expression (25.2%) was associated with ERG overexpression (P = 0.0036). SPOP mutations were found in 5.4% cases, all with wild-type (wt) ERG (P = 0.007). FOXA1 mutations were found in 8.2% cases, most of them ERG wt (P = 0.06). No IDH1 mutations were found. SPOP or FOXA1 mutations were found in 1.7% of ERG-rearranged, and 34.2% of non-ERG-rearranged cases (P < 0.0001). SPOP or FOXA1 alterations (mutations or expression loss) were significantly more common in GG5, while isolated ERG overexpression was more common in GG1 tumors (P = 0.042). SPOP-or FOXA1-mutated cases were associated with a shorter time to prostate-specific antigen (PSA) recurrence in the univariate (P = 0.0009), and with the PSA recurrence risk in the multivariate (P = 0.023) analysis. CONCLUSIONS: In conclusion, SPOP and FOXA1 mutations may have prognostic value in ERG wt tumors. Interestingly, in absence of SPOP mutations, downregulation of this gene is a feature of many ERG-rearranged prostate tumors.

Complementary value of electron microscopy and immunohistochemistry in the diagnosis of non-small cell lung cancer: A potential role for electron microscopy in the era of targeted therapy.

With the identification of therapeutic targets for lung adenocarcinoma, it has become mandatory to distinguish it from other entities. Some cases remain classified as non-small cell lung carcinoma, not otherwise specified (NSCLC-NOS) with immunohistochemistry. Electron microscopy (EM) can be useful, allowing the identification of glandular differentiation. The aim of this study was to determine the complementary value of immunohistochemistry and EM.Forty-eight NSCLC-NOS cases were selected (PSMAR-Biobank, Barcelona, Spain). Immunohistochemistry (TTF-1, p40) was performed. Tissue was retrieved from paraffin blocks. Results were compared to the final diagnosis, derived from combination of light microscopy, immunohistochemistry, EM, molecular studies and resection specimen.Immunohistochemistry concurred with final diagnosis in 36 cases (75%, Kappa = 0.517). EM agreed with final diagnosis in 35 (72.9%, Kappa = 0.471). Immunohistochemistry had a sensitivity = 73%, specificity = 100%, positive predictive value (PPV) = 100% and negative predictive value (NPV) = 52.4% for adenocarcinoma. All adenocarcinoma cases not solved by immunohistochemistry (n = 10) were classified by EM, and vice versa. Data from EM were identical to those of immunohistochemistry: sensitivity = 73%, specificity = 100%, PPV = 100% and NPV = 52.4%. Combining both techniques, 47 cases were coincident with final diagnosis (97.9%, Kappa = 0.943).EM can provide valuable information in subtyping NSCLC-NOS, being particularly useful when immunohistochemistry is inconclusive. EM could be considered as a complementary tool for decision-making in NSCLC-NOS.

Cell and tissue interactions of Treponema pallidum in primary and secondary syphilitic skin lesions: an ultrastructural study of serial sections.

There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.

Immunohistochemical markers as predictors of prognosis in multifocal prostate cancer.

The impact of tumor focality on prostate cancer (PCa) prognosis has been addressed in several studies with conflicting results. Tumor foci from multifocal (MF) PCa can show highly heterogeneous molecular features. Our aim was to analyze the protein expression of PTEN, SPOP, SLC45A3, ETV1, ERG and the "triple hit" (ERG overexpression, PTEN plus SLC45A3 loss) in unifocal (UF) and MF PCa, to evaluate their value as prognostic markers according to focality, and the role of tumor heterogeneity in MF disease. PTEN, SPOP, SLC45A3, ETV1 and ERG immunohistochemical expression was evaluated in 185 PCa from 9 TMAs, 51 UF and 134 MF. In a subset of 69 MF cases, the dominant and secondary foci (DF and SF) were compared. Heterogeneity was considered when both tumor foci presented different expression patterns. Relationship with clinicopathological features was also analyzed. MF PCa was diagnosed in significantly younger patients when compared to UF ones (p = 0.007). ETV1 overexpression was associated with UF disease (p = 0.028). A shorter time to PSA recurrence was related to SLC45A3 wt expression in UF PCa (p = 0.052), and to SPOP expression loss (p = 0.043) or "triple hit" phenotype in MF PCa (p = 0.041). In MF cases, PTEN loss, SLC45A3 loss and "triple hit" phenotype were associated with the DF and had significant heterogeneity. In conclusion, our results indicate that UF and MF PCa have relevant and consistent molecular differences. The analysis of an immunohistochemical panel, composed by PTEN, SPOP, SLC45A3, ETV1 and ERG, could be useful to predict outcome in MF cases.

Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors.

Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context. Methods: We generated transgenic mice with an endothelial-specific and inducible Snail1 depletion. This murine line was crossed with MMTV-PyMT mice that develop mammary gland tumors and the consequence of Snail1 depletion in the endothelium were investigated. We also interfere Snail1 expression in cultured endothelial cells. Results: Specific Snail1 depletion in the endothelium of adult mice does not promote an overt phenotype; however, it delays the formation of mammary gland tumors in MMTV-PyMT mice. These effects are associated to the inability of Snail1-deficient endothelial cells to undergo angiogenesis and to enhance CAF activation in a paracrine manner. Moreover, tumors generated in mice with endothelium-specific Snail1 depletion are less advanced and show a papillary phenotype. Similar changes on onset and tumor morphology are observed by pretreatment of MMTV-PyMT mice with the angiogenic inhibitor Bevacizumab. Human breast papillary carcinomas exhibit a lower angiogenesis and present lower staining of Snail1, both in endothelial and stromal cells, compared with other breast neoplasms. Furthermore, human breast tumors datasets show a strong correlation between Snail1 expression and high angiogenesis. Conclusion: These findings show a novel role for Snail1 in endothelial cell activation and demonstrate that these cells impact not only on angiogenesis, but also on tumor onset and phenotype.

Genomic Predictors of Good Outcome, Recurrence, or Progression in High-Grade T1 Non-Muscle-Invasive Bladder Cancer.

High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer with unpredictable outcome and poorly understood risk factors. Here, we examined the association of somatic mutation profiles with nonrecurrent disease (GO, good outcome), recurrence (R), or progression (PD) in a cohort of HGT1 patients. Exome sequencing was performed on 62 HGT1 and 15 matched normal tissue samples. Both tumor only (TO) and paired analyses were performed, focusing on 95 genes known to be mutated in bladder cancer. Somatic mutations, copy-number alterations, mutation load, and mutation signatures were studied. Thirty-three GO, 10 R, 18 PD, and 1 unknown outcome patients were analyzed. Tumor mutational burden (TMB) was similar to muscle-invasive disease and was highest in GO, intermediate in PD, and lowest in R patients (P = 0.017). DNA damage response gene mutations were associated with higher TMB (P < 0.0001) and GO (P = 0.003). ERCC2 and BRCA2 mutations were associated with GO. TP53, ATM, ARID1A, AHR, and SMARCB1 mutations were more frequent in PD. Focal copy-number gain in CCNE1 and CDKN2A deletion was enriched in PD or R (P = 0.047; P = 0.06). APOBEC (46%) and COSMIC5 (34%) signatures were most frequent. APOBEC-A and ERCC2 mutant tumors (COSMIC5) were associated with GO (P = 0.047; P = 0.0002). pT1b microstaging was associated with a genomic cluster (P = 0.05) with focal amplifications of E2F3/SOX4, PVRL4, CCNE1, and TP53 mutations. Findings were validated using external public datasets. These findings require confirmation but suggest that management of HGT1 bladder cancer may be improved via molecular characterization to predict outcome. SIGNIFICANCE: Detailed genetic analyses of HGT1 bladder tumors identify features that correlate with outcome, e.g., high mutational burden, ERCC2 mutations, and high APOBEC-A/ERCC2 mutation signatures were associated with good outcome.

[Biochemical-histo-morphometric findings of the residual prostate (II): long-term PSA behavior after retropubic adenomectomy for BPH. Relationship with prostate volume, histology and its implications in the diagnosis of subsequent adenocarcinoma]. / Hallazgos bioquímico- histo- morfométricos de la próstata residual (II): comportamiento del PSA,A largo plazo, tras adenomectomía retropúbica por H.B.P. Interrrelaciones con el volumen e histología de la próstata residual y sus implicaciones en el diagnóstico ulterior de adenocarcinoma.

SUMMARY OBJECTIVES: To evaluate the changes experienced by the amount of PSA in patients diagnosed with BPH undergoing retropubic adenomectomy (with vesico-capsule plasty) in the short and long term, and the relationships between weight and /or prostate volume calculated preoperatively, volumes and histology of the surgical tissue and residual tissue remaining immediate and on the long term. METHODS: A consecutive series of 70 cases of BPH surgery and followed up beyond 5 years with preoperative PSA and transrectal ultrasound, histology of the piece, postoperative transrectal ultrasound, PSA annually until the fifth year and ultrasound. Within this group, residual prostate histology was obtained in 30 patients between 12 and 36 months after adenomectomy. RESULTS: In accordance to our own confirmed studies, the ATH (transcervical hemostatic adenomectomy) removes by enucleation 76% of the entire volume reported by preoperative ultrasound, including capsule. In our cases, PSA has dropped 83% at one year after surgery compared with the preoperative value, and in most cases that have already reached 5 years of follow-up, this percentage remains with little variation. Having being established a strong relationship between PSA and glandular volume, we must evaluate the need for new cut-off values giving more value to the PSA density in relation to the volume of residual prostate, attempting to improve early diagnosis of carcinoma in these particular cases, in which will be useful a new protocol design. CONCLUSIONS: PSA decline, histology of the prostate after adenomectomy and the morphometric changes after surgery and at mid-term, advise a more accurate value of PSA in patients who underwent open surgery, in order to detect a carcinoma in the residual prostate gland.

Strong cytoplasmic ETV1 expression has a negative impact on prostate cancer outcome.

Overexpression of ETS genes is involved in prostate cancer (PrCa), but there is little information on the non-ERG components of this family. We have investigated ETV1, ETV4, and ETV5 overexpression, with or without PTEN loss, and their association with grade group (GG), pathological stage, focality, and PSA recurrence in PrCa. ETS gene expression was analyzed by qPCR in 104 cases. ETV1 and PTEN immunohistochemistry was assessed in TMA sections from 194 additional cases (PSMAR-Biobank, Barcelona, Spain). ETS mRNA overexpression was found in 23.1%, being ETV1 the most frequently overexpressed (18.3%). ETV1 protein overexpression was detected in 30.4% cases (moderate in 19.6%, strong in 10.8%). PTEN protein expression loss was detected in 36.1% cases and was not associated with ETV1. Strong-moderate ETV1 protein overexpression reaches its highest values in GG3-4, whereas its negativity was significantly more common in GG1 tumors (p = 0.034). ETV1-overexpressing tumors were more often unifocal (p = 0.0007) and high stage (p = 0.032). PTEN loss was less common in GG1 (p = 0.012) and showed a trend to be less frequent in pT2 (p = 0.062) tumors. Strong ETV1 immunostaining (histoscore > 177) was associated with shorter time to PSA recurrence in the univariate (p = 0.002) and in the multivariate analysis (p = 0.018). Moreover, when strong ETV1 overexpression was not combined with PTEN loss, its association with PSA recurrence was even stronger (p = 0.0004). In conclusion, non-ERG ETS overexpression, particularly ETV1 overexpression, has a non-negligible role in PrCa. Strong ETV1 protein expression has a negative impact on prostate cancer outcome that seems to be independent of PTEN status.

Immunohistochemical expression of mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) in prostate cancer: correlation with grade groups (WHO 2016) and ERG and PTEN status.

The role of DNA MMR genes in prostate cancer (PrCa) is controversial, as genetic alterations leading to microsatellite instability are incompletely defined in these tumors. ERG rearrangements and PTEN loss are concomitant events in PrCa. The aim of this study has been to analyze the immunohistochemical (IHC) expression of MSH2, MSH6, MLH1, PMS2, ERG, and PTEN and their potential association with the grade group (GG) grading system (WHO 2016) and PSA recurrence in a series of 200 PrCa (PSMAR-Biobank, Barcelona, Spain). MSH2, MLH1, PMS2, and PTEN losses were documented in 8%, 5%, 2%, and 36.5%, respectively. ERG expression was found in 48%. MSH6 showed an increase of expression with respect to basal levels in 42.1% of the cases. A statistical association between MSH6 overexpression and GG5 was found (p = 0.0281). ERG-wild-type cases were associated with single MSH2 loss (p = 0.024), and MSH2 and/or MLH1 loss (p = 0.019). The percentage of cases with PTEN loss was 20.5% (8/39) in GG1, 37.6% (53/141) of clustered GG2 to 4, and 60% (12/20) of GG5 (chi-square test, p = 0.01). Thus, PTEN expression loss was statistically more frequent in the upper-grade tumors. PMS2 loss was an infrequent event, but it was statistically associated with shorter time to PSA recurrence (p = 0.011). These results suggest the existence of an alternative non-ERG pathway associated with MSH2 or MLH1 expression loss. MSH6 overexpression could be a marker of aggressiveness in PrCa. The IHC assessment of DNA MMR proteins, ERG and PTEN, could identify different altered PrCa pathways, which could aid patient stratification.

Sebaceous Differentiation in Squamous Cell Carcinoma of the Larynx and Adjacent Pharynx: Case Report with Review and Discussion of the Literature.

Among the variants of squamous cell carcinoma (SCC) of the head and neck arising in mucosal surfaces, examples with sebaceous differentiation are exceedingly rare. We present a new case of SCC with sebaceous differentiation, developing in the larynx of a 64 year-old male, cigarette smoker and alcohol drinker. The tumor extended transglottically, metastasized to cervical lymph nodes, and killed the patient after 12 months. Comparing this case with four previously reported cases of SCC with sebaceous differentiation, two arising in the larynx and the other two in the adjacent pharynx, all five patients mostly shared the following features: appearance of the tumor in the seventh decade of life, heavy tobacco smoking, alcohol intake in three, surgery as mainstay treatment, tumor size between 2 and 4.7 cm, and regional lymph node metastases in four of them. Out of the four patients with a follow up of 12 months, two died of disease, one was alive with disease, and only one was alive without disease. One patient was lost for follow up. In conclusion, mucosal SCC with sebaceous differentiation is a very rare variant of SCC that when arising in the larynx and anatomically adjacent parts of the pharynx behaves aggressively and bears a dismal prognosis. The recognition of new cases of this entity requires special awareness of its phenotypic features and may be important for further assessment of its behavior.

ERG overexpression plus SLC45A3 (prostein) and PTEN expression loss: Strong association of the triple hit phenotype with an aggressive pathway of prostate cancer progression.

TMPRSS2 and SLC45A3 rearrangements may coexist in the same tumor. ERG rearrangements and PTEN loss are concomitant events in prostate cancer (PrCa), and can cooperate in progression. We have reported that mRNA expression of TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss define an aggressive tumor subset. The aim of this study has been to validate these results by immunohistochemistry in a large cohort of tumors. ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain). ERG protein expression was found in 46.8% and SLC45A3 and PTEN loss in 30% and 34% tumors, respectively. Single ERG positive immunostaining was associated with GS = 6 tumors (p = 0.016), double ERG+/PTEN loss with GS = 7 (p = 0.008) and Grade Group 2 (GG) or GG3 cases (p = 0.042), ERG+/SLC45A3 loss/PTEN loss ("triple hit") with GS ≥ 8 (p < 0.0001) and GG4 or GG5 tumors (p = 0.0003). None of GS = 6 nor = GG1 cases showed this combination. In the GS ≥ 8 group, ERG+ (p = 0.002), PTEN loss (p = 0.009) and "triple hit" (p = 0.003) were associated with Gleason pattern 3 component, and single SLC45A3 loss (p = 0.036) with GS ≥ 8 without pattern 3. The number of aberrant events and the triple hit were strongly associated with shorter PSA progression-free survival. In GS = 6 PrCa, single ERG+ was also associated with progression. ERG+ identifies a distinct pathway of PrCa. Additional assessment of PTEN and SLC45A3 adds relevant prognostic information. The triple hit phenotype (ERG+/SLC45A3 loss/PTEN loss) is associated with progression and could be used for patient stratification, treatment and follow-up.

Extrathoracic mesothelial proliferations and their mimics.

Mesothelial proliferations, either reactive or neoplastic in nature, often pose difficult diagnostic dilemmas. Electron microscopy continues to be a gold standard in the identification of mesothelial differentiation. However, it is very common to apply long panels of antibodies for that purpose. In most cases, light microscopy and immunohistochemistry will solve the problem. However, the definitive, specific, and sensitive immunohistochemical marker is still lacking. This is particularly true in peritoneal and testicular mesothelial tumors, in which common embryologic origin with epithelial elements results in overlapping immunohistochemistry and morphology. The particularities of peritoneal and testicular mesothelial proliferations, and the main tumors that may mimic them in these sites, as well as the value and limitations of immunohistochemistry and electron microscopy in their differential diagnosis are the subject of this review.

Vulvar angiomyxoma, aggressive angiomyxoma, and angiomyofibroblastoma: an immunohistochemical and ultrastructural study.

To investigate the histogenetical unifying theory of a single, pluripotential primitive cell for vulvar angiomyxoma, aggresive angiomyxoma, and angiomyofibroblastoma, an optical, immunohistochemical and ultrastructural study of a superficial angiomyxoma, aggressive angiomyxoma, and angiomyofibroblastoma was performed. These three tumors showed immunohistochemical and ultrastructural overlapping features. The results of the study suggest that these three tumor entities probably arise on a common pluripotential primitive cell located around the vessels of connective tissue, which could show the capacity for modulating its penotype toward similar but distinct mature cell types.

CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection.

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.

The current role of electron microscopy in the diagnosis of epithelial and epithelioid tumors.

Electron microscopy may be applied to the study of epithelial or epithelial-like tumors with benefits similar to those encountered when it is applied to other diseases. Thus, it may complement and allow us to understand the light microscopic appearance of tumors, help in tailoring or reducing the number of antibodies, or lead to diagnosis in cases with paradoxical or nonspecific immunocytochemical results. An important, newly suggested application is to use it as a quality assurance tool in the evaluation of cases already diagnosed by other methods. Tumors with epithelial phenotype are highly prevalent, and therefore the number of problem cases can also be relatively high. In this article, we review the main ultrastructural features used in the differential diagnosis of epithelial and epithelioid tumors and some potential pitfalls. In addition, we summarize the criteria for differential diagnosis in specific topographical areas and analyze some examples of how electron microscopy may improve the accuracy of pathological diagnosis by interacting with currently available immunocytochemical panels.

[Histomorphometric findings in the residual prostate and prostatic hollow after retropubic surgery for BPH: (I) baseline data obtained from the last 70 consecutive cases]. / Hallazgos histomorfométricos de la próstata residual y celda prostática tras la cirugía retropúbica por H.B.P.: (I) datos basales obtenidos en los últimos 70 casos consecutivos.

OBJECTIVES: To present the data obtained from surgical specimens and biopsies of residual prostate and prostatic capsule, which in addition to the information provided by imaging tests give us the baseline situation of the prostatic surgical bed and residual prostate after transcervical hemostatic adenomectomy with capsule plasty. All this is the first step for the long-term study of its evolution and possible implications in the genesis of new obstructive or neoplastic pathology. METHODS: 70 consecutive cases of transcervical hemostatic adenomectomy with the variation of capsule plasty, recently developed, after a previous experience of 1033 retropubic surgeries. We analyze the histologic findings in surgical specimens, biopsies of residual gland and prostate capsule, and confirmed the immediate changes surgery causes, measuring the volumes of residual prostate by ultrasound. As the base for comparisons we analyzed residual prostates from prostatectomies or radical cystoprostatectomy specimens in "young" patients. RESULTS/CONCLUSIONS: We obtained objective data about predominant and associated histological lesions found in adenomectomy specimens. In the same way, the same data were obtained from biopsies of peripheral residual prostate together with the volume of such zone, which should establish, if our hypothesis is right, the mid-long-term prognostic criteria for the approach to the so-called post operative reexpansion of the prostatic hollow and the possible establishment of new obstructive pathology.

[Report of two cases of bladder and prostate oat cell tumors]. / "Presentación de dos casos: vesical y prostático de oat-cell".

OBJECTIVES: To report two cases of bladder and prostate oat cell tumors with bad outcome, in accordance to the bibliographic review. METHODS: The case in the bladder was associated with squamous differentiation and adenocarcinoma. Radical treatment followed by adjuvant chemotherapy did not stop the fatal outcome which ended 13 months later in acute septicemia having developed multiple metastases. The case in the prostate presented as oliguria-anuria and bilateral hydronephrosis which required the placement of a nephrostomy tube in an emergency basis. Once diagnosis was achieved the extemal urinary diversion was converted to intemal to improve patient's comfort. There was no response to systemic chemotherapy and the patient died 4 months after diagnosis. CONCLUSIONS: These cases add to the rare presence of this pathology in the bibliography. In our country, 15 cases have been confirmed in the bladder and 5 in the prostate; around the world, 150 and 59 respectively. Although there is a certain tendency to think that radical treatment and chemotherapy is the least bad of the options, some consequences of conservative attitudes offer similar results, mainly when preserving the bladder.

Hallazgos bioquímico-histomorfométricos de la prostata residual (II): Comportamiento del PSA,a largo plazo, tras adenomectomia retropubica por H.B.P. Interrrelaciones con el volumen e histología de la prostata residual y sus implicaciones en el diagnostico ulterior de adenocarcinoma / Biochemical–histo-morphometric findings of the residual prostate (II): Long-term PSA behavior after retropubic adenomectomy for BPH. Relationship with prostate volume, histology and its implications in the diagnosis of subsequent adenocarcinoma

OBJETIVO: Constatar las variaciones experimentadas por la cifra de PSA en pacientes diagnosticados de HBP y sometidos a adenomectomía retropúbica (A.T.H. con vesicocapsuloplastia) a corto y largo plazo y las relaciones existentes entre aquella, los pesos y/o volúmenes prostáticos calculados en el preoperatorio, los volúmenes e histología de la pieza quirúrgica y del tejido residual inmediatos y lejanos.MÉTODO: Lo constituyen una serie inical de 70 casos de HBP consecutivos sometidos a cirugía y seguidos hasta más allá de los 5 años con PSA y ecografías transrectales preoperatorias, histología de la pieza, ecografía transrectal postoperatoria , PSA anual hasta el quinto año, según los casos, y ecografía postoperatoria lejana discrecional. Dentro de este grupo, en 30 pacientes, se obtuvo histología de la próstata residual entre 12 y 36 meses post adenomectomía.RESULTADOS: Según estudios propios, ya confirmados, la ATH (adenomectomía transcervical hemostática) extirpa la hiperplasia por enucleación representando el 76% de todo el volumen preoperatorio que informa la ecografía, incluyendo cápsula. A su vez, en nuestros casos, el PSA ha descendido, al año de la cirugía, una media del 83% con relación al preoperatorio y, en la mayoría de los casos que ya han alcanzado los 5 años de seguimiento, ese porcentaje se mantiene sin apenas variación. Establecida una fuerte relación entre PSA y volumen glandular hay que plantearse la necesidad de redeterminar las cifras de “cut-off” dando más valor a la PSA density del mismo en relación con los volúmenes reducidos de la próstata residual en un intento por mejorar el diagnóstico precoz de un carcinoma de la misma para lo que será útil el diseño de un nuevo protocolo(AU)

CONCLUSIÓN: El descenso del PSA, la histología de la próstata tras la adenomectomía y los morfométricos cambios tras la cirugía y a medio plazo aconsejan una más adecuada definición del nivel de corte del PSA en estos pacientes en orden a detectar más precozmente un carcinoma en la próstata residual(AU)

OBJECTIVES: To evaluate the changes experienced by the amount of PSA in patients diagnosed with BPH undergoing retropubic adenomectomy (with vesico-capsule plasty) in the short and long term, and the relationships between weight and / or prostate volume calculated preoperatively, volumes and histology of the surgical tissue and residual tissue remaining immediate and on the long term.METHODS: A consecutive series of 70 cases of BPH surgery and followed up beyond 5 years with preoperative PSA and transrectal ultrasound, histology of the piece, postoperative transrectal ultrasound, PSA annually until the fifth year and ultrasound. Within this group, residual prostate histology was obtained in 30 patients between 12 and 36 months after adenomectomy.RESULTS: In accordance to our own confirmed studies, the ATH (transcervical hemostatic adenomectomy) removes by enucleation 76% of the entire volume reported by preoperative ultrasound, including capsule. In our cases, PSA has dropped 83% at one year after surgery compared with the preoperative value, and in most cases that have already reached 5 years of follow-up, this percentage remains with little variation. Having being established a strong relationship between PSA and glandular volume, we must evaluate the need for new cut-off values giving more value to the PSA density in relation to the volume of residual prostate, attempting to improve early diagnosis of carcinoma in these particular cases, in which will be useful a new protocol design.CONCLUSIONS: PSA decline, histology of the prostate after adenomectomy and the morphometric changes after surgery and at mid-term, advise a more accurate value of PSA in patients who underwent open surgery, in order to detect a carcinoma in the residual prostate gland(AU)