Penile Lichen Sclerosus and "Nevus Elasticus".

The association between penile lichen sclerosus and striking accumulation of elastic fibers in deep dermis has been described in rare reports, mostly in vulvar lesions. We describe one case of severe balanopreputial adhesions related to lichen sclerosus and this form of elastosis, with no concomitant neoplasia. Aggregates of elastic fibers were seen in deep dermis and in blood vessels. The lesion mirrors nevus elasticus and nevus elasticus vascularis - a well described cutaneous lesion with no known association with lichen sclerosus.

Seroprevalence and risk factors associated with equineleptospirosis in the metropolitan region of Salvador and Recôncavo Baiano region, Bahia state (NE Brazil).

Equine leptospirosis, although usually asymptomatic, has been associated with recurrent uveitis, abortion, and other systemic signs, constituting a major economic loss in the equine agribusiness sector. The occurrence of anti-Leptospira spp. agglutinins were investigated in 1200 serum samples of horses from 27 municipalities of the Recôncavo Baiano region, Bahia state (NE Brazil), besides the risk factors related to animals and their cattle farms. The microscopic agglutination test (MAT) was performed using 13 serogroups of Leptospira spp. as antigens. From 1200 analyzed equines, 97 (8%) were considered as positive, which obtained titer equal to or higher than 200. In 22 (78.6%) from the 28 properties, at least one animal was detected as seropositive. The most prevalent serogroup in animals, raised in stables, was the Australis (serovar Bratislava) 67%; in mounted police animals was the Sejroe (serovar Wolffi and Hardjobovis) 50%; and equestrian animals was the Australis (serovar Bratislava) 25% and Icterohaemorrhagiae (serovar Copenhageni) 25%. Equine leptospirosis is present in most cattle farms of the region studied. The risk factors of major importance regarded the semi-extensive livestock farming, the land topography of the cattle farm, the contact with animals in neighboring properties, and cohabitation with goats.

Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases.

AIMS: To further characterise biphasic squamoid renal cell carcinoma (RCC), a recently proposed variant of papillary RCC. METHODS AND RESULTS: We identified 28 tumours from multiple institutions. They typically showed two cell populations-larger cells with eosinophilic cytoplasm and higher-grade nuclei, surrounded by smaller, amphophilic cells with scanty cytoplasm. The dual morphology was variable (median 72.5% of tumour, range 5-100%); emperipolesis was found in all cases. The male/female ratio was 2:1, and the median age was 55 years (range 39-86 years). The median tumour size was 20 mm (range 9-65 mm). Pathological stage pT1a was found in 21 cases, pT1b in three, and pT3a and pT3b in one each (two not available). Multifocality was found in 32%: multifocal biphasic RCC in one case, biphasic + papillary RCC in two cases, biphasic + clear cell RCC in three cases, biphasic + low-grade urothelial carcinoma of the renal pelvis in one case, and biphasic + Birt-Hogg-Dubé syndrome in one case. Positive immunostains included: PAX8, cytokeratin (CK) 7, α-methylacyl-CoA racemase, epithelial membrane antigen, and vimentin. Cyclin D1 was expressed only in the larger cells. The Ki67 index was higher in the larger cells (median 5% versus ≤1%). Negative stains included: carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20; CD10 and 34ßE12 were variably expressed. Gains of chromosomes 7 and 17 were found in two evaluated cases. Follow-up was available for 23 patients (median 24 months, range 1-244 months): 19 were alive without disease, one was alive with recurrence, and one had died of disease (two had died of other causes). CONCLUSIONS: Biphasic papillary RCC is a rare variant of papillary RCC, and is often multifocal.

Prognostic pathological factors in radical cystectomy after neoadjuvant chemotherapy.

AIMS: We undertook a systematic evaluation of the prognostic value of numerous histological factors in 165 radical cystectomies (RCs) of patients with invasive urothelial carcinoma (UC) who underwent surgery after neoadjuvant chemotherapy (NAC). METHODS AND RESULTS: Tumour regression grade (TRG) and therapy-related stromal and epithelial changes were also recorded. Locally advanced disease (≥pT2 and/or pN+) was present in 64% of patients, 22% had no evidence of residual carcinoma (pT0 + pN0), and 28% had no evidence of residual muscle-invasive carcinoma (≤pT1 + N0). TRG1, TRG2 and TRG3 were found in 32%, 15% and 50% of patients, respectively. Histological variants of UC were reported in 25% of cases. The most common therapy-related stromal change was fibroblastic reaction (78%), and the most common epithelial change in residual UC was smudgy and poorly preserved chromatin (28%). Prominent stromal and epithelial changes were noted in 41% and 5% of RCs, respectively. Progression was found in 45% of patients, and cancer-related deaths occurred in 30%. Multivariate analysis showed that the only independent prognostic parameters for progression were T stage, N stage, lymphovascular invasion, and margin status. Similarly, only T stage, N stage and margin status correlated with cancer-related deaths. Neither TRG nor any of the stromal-related or epithelial-related variables correlated with outcome. CONCLUSIONS: We confirm that the traditional and routinely reported histological parameters in RC post-NAC remain the most powerful prognosticators of disease course. The significance of TRG in the bladder remains unconfirmed.

The Gleason pattern 4 in radical prostatectomy specimens in current practice - Quantification, morphology and concordance with biopsy.

PURPOSE: The upgrading of a prostate acinar adenocarcinoma grade group 1 (GG1) between needle biopsy and prostatectomy is common. The extent of high-grade tumor and cribriform morphology are currently suggested as prognostic factors. METHODS: We reviewed 159 prostatectomy specimens from a private laboratory and an academic/public institution in Salvador, Bahia. RESULTS: Tumors signed as GG1 at biopsy were upgraded in 59% of all cases. These tumors showed a low frequency of non-focal extraprostatic extension (one case, 3%), extensive positive surgical margins (two cases, 6%) and seminal vesicle invasion (one case, 3%). Among GG2 and GG3 tumors at prostatectomy, the percentage of Gleason pattern 4 (Gp4) involving the gland at ≤1%, 2-5% and >5% was associated with extensive extraprostatic extension (9%, 8% and 42%, respectively) and seminal vesicle invasion (1%, 10% and 31%, respectively). The volume of Gp4 of ≤1ml, >1 to 2ml and >2ml was associated with extensive extraprostatic extension (8%, 26% and 38%, respectively), seminal vesicle invasion (2%, 21% and 33%, respectively) and non-focal positive surgical margins (12%, 26% and 29%, respectively). Some GG2 tumors (~20%) indeed showed at least one measurement of Gp4 higher than one quarter of GG3 carcinomas. Cribriform morphology showed no significant associations for other adverse pathologic prognostic factors. CONCLUSION: Upgrading from GG1 to GG2 is associated with a very low frequency of morphologic features associated with poor prognosis. Routine quantification of Gp4 is feasible in radical prostatectomy products and seems to better stratify tumors regarding the association with other morphologic parameters of prognostic importance.

Global Gleason grade groups in prostate cancer: concordance of biopsy and radical prostatectomy grades and predictors of upgrade and downgrade.

AIMS: To evaluate concordance, upgrades and downgrades from biopsy to prostatectomy, and associated clincopathological parameters, using the recently proposed Gleason grade groups/International Society of Urologic Pathology (ISUP) grades. METHODS AND RESULTS: We evaluated 2529 patients who underwent biopsy and prostatectomy in our institution from 2005 to 2014. A global grade group (GR)/Gleason score (GS) was used. Factors associated with GR1/GS ≤6 upgrades and GR2/GS3 + 4 downgrades were analysed by multivariable logistic regression. The final GR/GS was identical with the biopsy GR/GS in 59.3% of cases, with the highest concordance for GR2 and GR5 and lowest for GR4. In GR1-5, identical grades were found in GR: (i) 47.6%, (ii) 73.6%, (iii) 52.8%, (iv) 21.4% and (v) 68.3%, respectively. Final GR was upgraded in 32.3% cases; in GR1-4: (i) 52.4%, (ii) 19.0%, (iii) 16.4% and (iv) 32.9%. Most frequent upgrades occurred from biopsy GR1 to prostatectomy GR2. A final GR downgrade was found in 8.3% cases. For individual GR2-5 the downgrades were found in GR: (i) 7.4%, (ii) 30.8%, (iii) 45.7% and (iv) 31.7%. Upgrades of biopsy GR1 were associated with: age ≥60 years, PSA density ≥0.2, ≥2 positive cores, ≥5% core tissue involvement and perineural invasion [area under receiver operating characteristic (ROC) curve 0.699]. Downgrades of biopsy GR2 correlated inversely with: age ≥60 years, PSA >10 ng/ml and ≥2 positive core (area under ROC curve 0.623). CONCLUSIONS: We found highest concordance for GR2 and GR5 and lowest for GR4. The baseline clinical variables associated with GR1 upgrades and GR2 downgrades may play a role in clinical decision-making.

Segmental absence of intestinal musculature -presentation in a 10-year-old boy with an extensive involved segment.

Segmental absence of the intestinal musculature is a rare cause of acute abdomen most likely associated with intestinal perforation and sepsis in neonates and adults. We present a case of a 10-year-old boy who developed acute abdomen and was treated with right hemicolectomy and partial resection of the ileum. The ileum showed a 20-cm-long stenotic segment showing prominent thinning of the intestinal wall. This case occurred in an older child, which appears to be rare when comparing the literature. The bowel defect was also the largest described to date, indicating the potential effect of an atonic segment leading to obstructive disease.

Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis.

Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.

Clear Cell Papillary Renal Cell Tumors: A Study of 42 Tumors with Emphasis on the Fibrous Capsule, Cystic Component, and GATA3 Immunohistochemistry.

Clear cell papillary renal cell tumor is a common and sometimes underdiagnosed renal cell neoplasm. Its proper recognition is important because its diagnosis implies a remarkably high probability of indolent behavior. This study aimed to evaluate the frequency of a fibrous capsule, a cystic component, and a GATA3 expression in clear cell papillary renal cell tumors. We assessed 419 renal cell neoplasms from three institutions located in northeastern Brazil and identified 42 clear cell papillary renal cell tumors (from 39 patients), which were the fourth most common renal cell neoplasm. These tumors commonly exhibited fibrous capsules (all showed complete or partial capsules) and cystic component (93%). Eighteen out of 42 tumors (43%) showed some expression of GATA3, and weak and focal staining was common among the positive tumors. Clear cell papillary renal cell tumor must always be included in the differential diagnosis of predominantly cystic renal cell neoplasms. As GATA3 is inconsistently expressed in clear cell papillary renal cell tumors, it is not useful in this diagnosis.

Analysis of false positive PI-RADS 4 lesions: experience from a single nonacademic center using cognitive fusion.

BACKGROUND: We evaluated pathological findings in targeted biopsies of PI-RADS4 and PI-RADS5 lesions, and clinical data that could predict those patients with benign findings. MATERIALS AND METHODS: A retrospective study was conducted to summarize the experience from a single nonacademic center using cognitive fusion and a 1.5 or 3.0 Tesla scanner. RESULTS: We found a false positive rate of 29 and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Diverse histologic patterns were observed among target biopsies. At multivariate analysis, size ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The small number of false PI-RADS5 lesions precluded further analyses. CONCLUSION: Benign findings are common in PI-RADS4 lesions and most of them do not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict a higher probability of false positive results in patients with PI-RADS 4 lesions.

Renal epithelioid angiomyolipoma with epithelial cysts: demonstration of Melan A and HMB45 positivity in the cystic epithelial lining.

Renal angiomyolipoma (AML) may present as rare variants such as epithelioid and AML with epithelial cysts posing difficulties for the diagnosis to the surgical pathologist. We report a case of a 46-year-old male patient presenting a 5-cm solid tumor in the lower pole of the left kidney, with cystic changes at cut surface. The tumor exhibited 95% of epithelioid cells with atypical nuclei. A small focus of typical AML was observed. The immunoprofile of tumor cells was classical of AML including expression of melanocytic markers such as HMB45 and Melan A. We report the immunohistochemical study of the cystic component in an epithelioid AML. In contrast to the immunoreactivity reported in typical AML, the present case shows obvious expression of melanocytic markers in the cystic epithelial lining. This is strong evidence that these cysts are neoplastic and derived from AML, rather than entrapped native collecting duct epithelium.

The many faces of endometriosis.

Endometriosis is a common disease; however, unusual findings may cause diagnostic difficulties. We present herein three cases illustrating different morphological appearances of endometriosis: 1) endometriosis with atypical hyperplasia associated with bilateral ovarian carcinoma (mixed clear cell/endometrioid in the left ovary and endometrioid in the right ovary); 2) deep infiltrating endometriosis with intravascular spread, polypoid configuration in peritoneal surfaces, and involvement of a lymph node; and 3) decidualized endometriosis with prominent myxoid/mucinous change and multivacuolated (pseudoxanthoma) cells. Awareness of uncommon morphological manifestations of endometriosis is important to avoid improper consideration of malignancy.

Attenuated nephritis in inducible nitric oxide synthase knockout C57BL/6 mice and pulmonary hemorrhage in CB17 SCID and recombination activating gene 1 knockout C57BL/6 mice infected with Leptospira interrogans.

The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene (Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. The animals used were Inos KO mice, recombination activating gene 1 (Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The frequency and severity of nephritis was significantly lower in the Inos KO mice. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10(7) and 10(6) leptospires, respectively. There was no evidence of PH in the WT controls. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. Of note, the absence of functional B- and T-cell lymphocytes did not preclude the occurrence of PH. These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables.

Immunotherapy targeting the PD-1-PD-L1 axis yielded good results in treating different immunologically ''hot'' tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11-41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41-50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.

Calcaneal chondroblastoma with secondary aneurysmal bone cyst: a case report.

We present a case of destructive chondroblastoma associated with secondary aneurysmal bone cyst involving the left calcaneus. Because of the extensive destruction of the calcaneus, total calcanectomy was the treatment of choice.

Real life data of MRI-targeted biopsy - experience from a single nonacademic centre using cognitive fusion and 1.5 tesla scanning.

OBJECTIVES: To date, it is unknown whether systematic biopsies can be safely omitted in patients with unsuspicious MRI findings or if systematic biopsies should be required when targeting focal lesions (PI-RADS 3-5). METHODS: A series of 366 patients (249 without a previous biopsy) were examined in a 1.5 Tesla MRI scanner. All patients were submitted to systematic biopsies (12-14 regions) with additional targeted biopsies (by cognitive fusion) of focal PI-RADS lesions (PI-RADS 3-5). RESULTS: In our series, patients with PI-RADS 1/2 findings had rates of adenocarcinoma of any grade, >GG1 and GG4/5 of 34%, 14% and 3%, respectively. The use of MRI prior to biopsy in our series increased the detection of clinically significant prostate cancer (CSPCa) in 28% of patients with focal lesions, and focal lesions were present in 293/366 (80%) of all patients. For CSPCa (>GG1), targeted biopsies improved the diagnosis in 28% of patients, while systematic biopsies resulted in an additional 19% of cancer cases in the series. CONCLUSION: Systematic biopsies should still be considered in patients with PI-RADS 1/2 findings. Our findings also suggest a stronger benefit of the combined strategy of targeted and systematic biopsies than the findings of previous studies concerning the detection of CSPCa in biopsy-naïve patients.

Metastatic parachordoma.

Tumors traditionally classified as parachordomas are rare, usually indolent, soft tissue neoplasms. This case report describes a 6-year-old girl with a mass in her left forearm measuring 11 x 6 cm. Foci of moderate nuclear atypia and various areas of necrosis were found in the tumor. Lung metastases were detected 3 months after diagnosis. Immunophenotyping revealed a strong, diffuse expression of pancytokeratin, S-100 protein, vimentin, glial fibrillary acidic protein and focal expression of chromogranin A. This is the fifth documented report on cases of metastasized parachordomas. It is rare for these neoplasms to show such aggressive behavior; moreover, immunoreactivity to chromogranin A is unexpected in these tumors. The relationship between the so-called parachordomas and soft tissue myoepithelioma/mixed tumors is discussed, including the recently defined pediatric myoepithelial carcinoma.

Chronic catastrophic-like antiphospholipid syndrome: a "smoldering" variant?

Catastrophic antiphospholipid syndrome (CAPS) is characterized by life-threatening diffuse thrombotic manifestations involving particularly small vessels of kidney, lungs, brain and skin. We report a 20-year-old female with systemic lupus erythematosus and secondary antiphospholipid syndrome who presented typical organ and histological involvement as seen in CAPS but with protracted course suggesting a "smoldering" form of the disease.

NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis.

Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19(+) expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4(+)CD25(high) T cell subset and the CD3(-)CD16(-)CD56(bright) NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.